Descriptor: "MESH: Immunologic Memory" - Searchworks@Jio Institute Digital Library Search Results

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64 results on '"MESH: Immunologic Memory"'

1. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author: Boris Novakovic, Andreas Schlitzer, Giuseppe Matarese, Zahi A. Fayad, Willem J. M. Mulder, Henk Stunnenberg, Andrew R. DiNardo, Niels P. Riksen, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Eva Kaufmann, Shabaana A. Khader, Michael H. Sieweke, Siroon Bekkering, Stephanie Fanucchi, Luis B. Barreiro, Maziar Divangahi, Mihai G. Netea, Reinout van Crevel, Jordi Ochando, Peter Aaby, Shruti Naik, Leo A. B. Joosten, Triantafyllos Chavakis, Musa M. Mhlanga, Eicke Latz, David L. Williams, Jos W. M. van der Meer, Luke A. J. O'Neill, Ramnik J. Xavier, Nigel Curtis, Robert W. Sauerwein, Kate L. Jeffrey, Edward R. Sherwood, Elaine Fuchs, Sebastian Weis, Nargis Khan, Melanie Hamon, Raphael Duivenwoorden, Keiko Ozato, Simone J.C.F.M. Moorlag, Jorge Domínguez-Andrés, Frank L. van de Veerdonk, Precision Medicine, ICMS Core, McGill University Health Center [Montreal] (MUHC), Bandim Health Project, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), Washington University in Saint Louis (WUSTL), The University of Chicago Medicine [Chicago], Radboud University Medical Center [Nijmegen], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Melbourne, Baylor College of Medicine (BCM), Baylor University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Eindhoven University of Technology [Eindhoven] (TU/e), University of Cape Town, Rockefeller University [New York], Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Harvard Medical School [Boston] (HMS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Trinity Biomedical Sciences Institute, School of Biochemistry & Immunology, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Bonn = University of Bonn, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Max Delbrück Centrum für Molekulare Medizin (MDC), University of Southern Denmark (SDU), Radboud University [Nijmegen], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Jena University Hospital [Jena], East Tennessee State University (ETSU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., Dinardo, A. R., Dominguez-Andres, J., Duivenwoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., Matarese, G., van der Meer, J. W. M., Mhlanga, M., Moorlag, S. J. C. F. M., Mulder, W. J. M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N. P., Sauerwein, R., Sherwood, E. R., Schlitzer, A., Schultze, J. L., Sieweke, M. H., Benn, C. S., Stunnenberg, H., Sun, J., van de Veerdonk, F. L., Weis, S., Williams, D. L., Xavier, R., Netea, M. G., Institut Pasteur [Paris], Consiglio Nazionale delle Ricerche (CNR), University of Bonn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, Radboud university [Nijmegen], Hamon, Melanie, and ACS - Atherosclerosis & ischemic syndromes
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], animal diseases, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Priming (immunology), Adaptive Immunity, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, ComputingMilieux_MISCELLANEOUS, immunology [BCG Vaccine], Vaccination, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Cell Differentiation, Common framework, [SDV] Life Sciences [q-bio], MESH: BCG Vaccine, BCG Vaccine, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH: Cell Differentiation, MESH: Immune Tolerance, Immunology, education, immunology [Adaptive Immunity], chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, Animals, Humans, ddc:610, Molecular Biology, MESH: Humans, immunology [Immune Tolerance], Cell Biology, MESH: Vaccination, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, immunology [Immunologic Memory], immunology [Immunity, Innate], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, bacteria, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Immunologic Memory, MESH: Adaptive Immunity, 030215 immunology
Abstract: The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.
Published: 2021
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2. Tissue-resident CD8 + T cells drive compartmentalized and chronic autoimmune damage against CNS neurons

Author: David Frieser, Aurora Pignata, Leila Khajavi, Danielle Shlesinger, Carmen Gonzalez-Fierro, Xuan-Hung Nguyen, Alexander Yermanos, Doron Merkler, Romana Höftberger, Virginie Desestret, Katharina M. Mair, Jan Bauer, Frederick Masson, Roland S. Liblau, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Université de Genève = University of Geneva (UNIGE), Medizinische Universität Wien = Medical University of Vienna, Mécanismes en sciences intégratives du vivant (MeLiS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Masson, Frédéric
Subjects: [SDV] Life Sciences [q-bio], MESH: Autoimmune Diseases* / pathology, MESH: CD8-Positive T-Lymphocytes, [SDV]Life Sciences [q-bio], MESH: Immunologic Memory, MESH: Central Nervous System, General Medicine
Abstract: The mechanisms underlying the chronicity of autoimmune diseases of the central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (TRM) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency of brain-infiltrating CD8+T cells exhibit a TRM-like phenotype in human autoimmune encephalitis. Using mouse models of neuronal autoimmunity and a combination of T single-cell transcriptomics, high-dimensional flow cytometry, and histopathology, we found that pathogenic CD8+T cells behind the blood-brain barrier adopt a characteristic TRMdifferentiation program, and we revealed their phenotypic and functional heterogeneity. In the diseased CNS, autoreactive tissue-resident CD8+T cells sustained focal neuroinflammation and progressive loss of neurons, independently of recirculating CD8+T cells. Consistently, a large fraction of autoreactive tissue-resident CD8+T cells exhibited proliferative potential as well as proinflammatory and cytotoxic properties. Persistence of tissue-resident CD8+T cells in the CNS and their functional output, but not their initial differentiation, were crucially dependent on CD4+T cells. Collectively, our results point to tissue-resident CD8+T cells as essential drivers of chronic CNS autoimmunity and suggest that therapies targeting this compartmentalized autoreactive T cell subset might be effective for treating CNS autoimmune diseases.
Published: 2022
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3. Robust and Functional Immune Memory Up to 9 Months After SARS-CoV-2 Infection: A Southeast Asian Longitudinal Cohort

Author: Hoa Thi My Vo, Alvino Maestri, Heidi Auerswald, Sopheak Sorn, Sokchea Lay, Heng Seng, Sotheary Sann, Nisa Ya, Polidy Pean, Philippe Dussart, Olivier Schwartz, Sovann Ly, Timothée Bruel, Sowath Ly, Veasna Duong, Erik A. Karlsson, Tineke Cantaert, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Communicable Disease Department [Phnom Penh] (CDC MOH), Ministry of Health [Mozambique], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The Howard Hughes Medical Institute (HHMI)–Wellcome Trust (208710/Z/17/Z to TC), « URGENCE COVID-19 » fundraising campaign of Institut Pasteur (TC, HA, and PD). HA is supported by the German Centre for International Migration and Development (CIM)., Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Vaccine Research Institute (VRI)
Subjects: CD4-Positive T-Lymphocytes, Immunology, MESH: Spike Glycoprotein, Coronavirus, CD8-Positive T-Lymphocytes, B cell immunity, Antibodies, Viral, MESH: Phosphoproteins, long term immune response, MESH: Antibodies, Neutralizing, MESH: Immunity, Cellular, Immunology and Allergy, Coronavirus Nucleocapsid Proteins, Humans, MESH: COVID-19, MESH: Coronavirus Nucleocapsid Proteins, MESH: SARS-CoV-2, MESH: Immunity, Humoral, B-Lymphocytes, Immunity, Cellular, MESH: Humans, T cell immunity, SARS-CoV-2, MESH: Cambodia, COVID-19, MESH: CD4-Positive T-Lymphocytes, RC581-607, Phosphoproteins, Antibodies, Neutralizing, MESH: CD8-Positive T-Lymphocytes, Immunity, Humoral, antibody effector function, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, Immunologic diseases. Allergy, Cambodia, Immunologic Memory, MESH: Antibodies, Viral
Abstract: The duration of humoral and cellular immune memory following SARS-CoV-2 infection in populations in least developed countries remains understudied but is key to overcome the current SARS-CoV-2 pandemic. Sixty-four Cambodian individuals with laboratory-confirmed infection with asymptomatic or mild/moderate clinical presentation were evaluated for Spike (S)-binding and neutralizing antibodies and antibody effector functions during acute phase of infection and at 6-9 months follow-up. Antigen-specific B cells, CD4+ and CD8+ T cells were characterized, and T cells were interrogated for functionality at late convalescence. Anti-S antibody titers decreased over time, but effector functions mediated by S-specific antibodies remained stable. S- and nucleocapsid (N)-specific B cells could be detected in late convalescence in the activated memory B cell compartment and are mostly IgG+. CD4+ and CD8+ T cell immune memory was maintained to S and membrane (M) protein. Asymptomatic infection resulted in decreased antibody-dependent cellular cytotoxicity (ADCC) and frequency of SARS-CoV-2-specific CD4+ T cells at late convalescence. Whereas anti-S antibodies correlated with S-specific B cells, there was no correlation between T cell response and humoral immune memory. Hence, all aspects of a protective immune response are maintained up to nine months after SARS-CoV-2 infection and in the absence of re-infection.
Published: 2022
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4. H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation

Author: Tiphaine M. N. Camarasa, Catherine Fitting, Melanie Hamon, Jean-Marc Cavaillon, Orhan Rasid, Christine Chevalier, Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris], Cytokines et Inflammation, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Work in the M.A.H. laboratory received financial support from Institut Pasteur and the French National Research Agency (ANR-EPIBACTIN). O.R. was supported by a stipend from the Pasteur – Paris University International PhD Program for part of this work. T.M.-N.C. is supported by a fellowship from the Foundation for Medical Research (Mariane Josso Prize)., We would like to thank Olivier Dussurget and Emmanuel Lemichez for the kind gift of the luminescent E. coli, Thomas Kohler and Sven Hammerschmidt for the S. pneumoniae strain, and Ignacio Santecchia for technical assistance with E. coli culture., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, MESH: Inflammation, Male, Adoptive cell transfer, Histone methyltransferase activity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Stimulation, NK cells, Systemic inflammation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, sepsis, Histones, Mice, 0302 clinical medicine, MESH: Animals, lcsh:QH301-705.5, Escherichia coli Infections, MESH: Histones, biology, MESH: Escherichia coli, NK cell memory, Cell biology, Killer Cells, Natural, Histone, Enhancer Elements, Genetic, MESH: Immunologic Memory, MESH: Immunity, Innate, medicine.symptom, epigenetic, MESH: Killer Cells, Natural, MESH: Interferon-gamma, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Interferon-gamma, medicine, Escherichia coli, Animals, Epigenetics, MESH: Mice, MESH: Escherichia coli Infections, Inflammation, Innate immune system, H3K4me1, Immunotherapy, MESH: Male, Endotoxemia, Immunity, Innate, 030104 developmental biology, lcsh:Biology (General), MESH: Endotoxemia, biology.protein, MESH: Enhancer Elements, Genetic, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: Summary: Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFNγ upon specific secondary stimulation. The NK cell memory response is detectable for at least 9 weeks and contributes to protection from E. coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation. : Rasid et al. show that sepsis-like systemic inflammation induces a type of long-lasting innate immune memory in NK cells, which can protect from E. coli infection. This is achieved by revealing an enhancer of IFNγ through histone monomethylation. Keywords: NK cells, NK cell memory, sepsis, epigenetic, H3K4me1
Published: 2019
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5. Cell-mediated immunity to NAGLU transgene following intracerebral gene therapy in children with Mucopolysaccharidosis type IIIB syndrome

Author: Gougeon, Marie-Lise, Poirier-Beaudouin, Béatrice, Ausseil, Jérome, Zérah, Michel, Artaud, Cécile, Heard, Jean-Michel, Deiva, Kumaran, Tardieu, Marc, Département Infection et Epidémiologie - Department of Infection and Epidemiology, Institut Pasteur [Paris], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Biothérapies pour les Maladies Neurodégénératives, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Neurologie Pédiatrique [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut Pasteur sponsored the study during thefirst 30 monthsand UniQure sponsored it for the following 36 months. Thestudy was supported by funds from the'Association FrançaiseContre les Myopathies (AFM)', the patients‘association'Vaincreles Maladies Lysosomales', the Institut Pasteur, the Conny MaevaCharitable Foundation, and a gift from the Akbaraly family., Institut Pasteur [Paris] (IP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, and Institut Pasteur sponsored the study during thefirst 30 monthsand UniQure sponsored it for the following 36 months. Thestudy was supported by funds from the'Association Française Contre les Myopathies (AFM)', the patients‘association'Vaincreles Maladies Lysosomales', the Institut Pasteur, the Conny MaevaCharitable Foundation, and a gift from the Akbaraly family.
Subjects: NAGLU, T-Lymphocytes, [SDV]Life Sciences [q-bio], Genetic Vectors, Immunology, MESH: Mucopolysaccharidosis III / complications, T cells, cellular immunity, Lymphocyte Activation, MESH: Immunity, Cellular, MESH: Acetylglucosaminidase / genetics, MESH: Genetic Therapy / adverse effects, Mucopolysaccharidosis III, MESH: Mucopolysaccharidosis III / genetics, MESH: Child, Acetylglucosaminidase, MESH: Acetylglucosaminidase / immunology, Humans, Transgenes, MESH: Lymphocyte Activation, Child, Original Research, Immunity, Cellular, Drug Administration Routes, MESH: Cytokines / metabolism, MESH: Genetic Therapy / methods, MESH: Genetic Vectors / administration & dosage, AAV, Genetic Therapy, RC581-607, cytokines, MESH: Drug Administration Routes, MESH: Genetic Vectors / genetics, MESH: Immunologic Memory, MPS IIIB, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic diseases. Allergy, CNS, Immunologic Memory
Abstract: International audience; Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. It was reported that AAV-mediated gene therapies might elicit a strong host immune response resulting in decreased transgene expression. To address this issue, we performed a comprehensive analysis of cellular immunity and cytokine patterns generated against the therapeutic enzyme in the four treated children over 5.5 years of follow-up. We report the emergence of memory and polyfunctional CD4+ and CD8+ T lymphocytes sensitized to the transgene soon after the start of therapy, and appearing in peripheral blood in waves throughout the follow-up. However, this response had no apparent impact on CNS transgene expression, which remained stable 66 months after surgery, possibly a consequence of the long-term immunosuppressive treatment. We also report that gene therapy did not trigger neuroinflammation, evaluated through the expression of cytokines and chemokines in patients' CSF. Milder disease progression in the youngest patient was found associated with low level and less differentiated circulating NAGLU-specific T cells, together with the lack of proinflammatory cytokines in the CSF. Findings in this study support a systematic and comprehensive immunomonitoring approach for understanding the impact immune reactions might have on treatment safety and efficacy of gene therapies.
Published: 2021
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6. CD4+CD8+ T-Lymphocytes in Xenogeneic and Human Graft-versus-Host Disease

Author: Kutaiba Alhaj Hussen, David Michonneau, Vincent Biajoux, Seydou Keita, Laetitia Dubouchet, Elisabeth Nelson, Niclas Setterblad, Helene Le Buanec, Jean-David Bouaziz, Fabien Guimiot, Gérard Socié, Bruno Canque, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'Hématologie biologique [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Paris Cité (UPCité)
Subjects: lcsh:Immunologic diseases. Allergy, CD3, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, MESH: Graft vs Host Disease, Hematopoietic stem cell transplantation, xenograft mouse model, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, graft-versus-host disease, Cytotoxic T cell, Immunology and Allergy, MESH: Animals, allogeneic hematopoietic stem cell transplantation, MESH: Mice, SCID, immunoregulatory diversion, MESH: Mice, MESH: Transplantation, Heterologous, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, CD4 + CD8 + T lymphocytes, 0303 health sciences, MESH: Cytokines, MESH: Humans, biology, MESH: CD4-Positive T-Lymphocytes, MESH: Programmed Cell Death 1 Receptor, medicine.disease, MESH: CD8-Positive T-Lymphocytes, MESH: Male, 3. Good health, [SDV] Life Sciences [q-bio], CTL, Graft-versus-host disease, surgical procedures, operative, CD4+CD8+ T lymphocytes, biology.protein, MESH: Immunologic Memory, lcsh:RC581-607, MESH: T-Lymphocytes, Cytotoxic, MESH: Female, CD8, 030215 immunology
Abstract: Mechanisms driving acute graft-versus-host disease (aGVHD) onset in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still poorly understood. To provide a detailed characterization of tissue-infiltrating T lymphocytes (TL) and search for eventual site-specific specificities, we developed a xenogeneic model of aGVHD in immunodeficient mice. Phenotypic characterization of xenoreactive T lymphocytes (TL) in diseased mice disclosed a massive infiltration of GVHD target organs by an original CD4+CD8+ TL subset. Immunophenotypic and transcriptional profiling shows that CD4+CD8+ TL comprise a major PD1+CD62L−/+ transitional memory subset (>60%) characterized by low level expression of cytotoxicity-related transcripts. CD4+CD8+ TL produce high IL-10 and IL-13 levels, and low IL-2 and IFN-γ, suggestive of regulatory function. In vivo tracking of genetically labeled CD4+ or CD8+ TL subsequently found that CD4+CD8+ TL mainly originate from chronically activated cytotoxic TL (CTL). On the other hand, phenotypic profiling of CD3+ TL from blood, duodenum or rectal mucosa in a cohort of allo-HSCT patients failed to disclose abnormal expansion of CD4+CD8+ TL independent of aGVHD development. Collectively, our results show that acquisition of surface CD4 by xenoreactive CD8+ CTL is associated with functional diversion toward a regulatory phenotype, but rule out a central role of this subset in the pathogenesis of aGVHD in allo-HSCT patients.
Published: 2020
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7. Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers

Author: Camille Sureau, Verena Hehle, Oriane Fiquet, Cyril Planchais, Valérie Lorin, Marie-Louise Michel, Jordan D. Dimitrov, Helene Strick-Marchand, Nadege Pelletier, Stanislas Pol, Maxime Beretta, Hugo Mouquet, Thierry Hieu, Malika Ait-Goughoulte, James P. Di Santo, Andrea Stauffer, Marie-Noëlle Ungeheuer, Maryline Bourgine, Benjamin Vesin, Solen Morisse, BOURGINE, Maryline, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, Human Antibody Responses to Viruses - HUMANTIVIRUSES - - EC:FP7:ERC2014-01-01 - 2018-12-31 - 337146 - VALID, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris] (IP), F. Hoffmann-La Roche [Basel], Immunité Innée - Innate Immunity, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Centre de Recherche Translationnelle - Center for Translational Science (CRT), H. Mouquet received core grants from the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR-10-LABX-69-01) and INSERM. This work was funded by Institut Roche. V. Hehle and M. Beretta were supported by postdoctoral fellowships from Roche. V. Hehle and T. Hieu were also supported by the European Research Council–Seventh Framework Program (ERC-2013-StG 337146). H. Strick-Marchand was supported by the Institut Pasteur and Agence Nationale de Recherches sur le Sida et les Hépatites Virales (2016-16365, 2019-19241)., We are grateful to members of the Center for Translational Sciences (Institut Pasteur), Cassandre Von Platen (Clinical core) for the preparation of the RAPIVIB protocol, and Gloria Morizot (Investigation Clinique et Accès aux Ressources Biologiques) for collecting biological samples and associated personal data. We also thank Sandrine Schmutz, Sophie Novault (UTechS CB, Center for Translational Sciences, Institut Pasteur), and Ayrin Kök for their technical help with single cell sorting, and Dr. J. Aguilar (Center for Genetic Engineering and Biotechnology, Havana, Cuba) for providing us with the purified adw HBsAg particles., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), École Pratique des Hautes Études (EPHE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)
Subjects: 0301 basic medicine, HBsAg, MESH: Epitopes, MESH: Hepatitis B, Chronic, Immunology, MESH: Flow Cytometry, Viremia, medicine.disease_cause, Epitope, Virus, MESH: Antibodies, Neutralizing, MESH: Cross Reactions, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, 0302 clinical medicine, MESH: B-Lymphocytes, medicine, Immunology and Allergy, MESH: Animals, MESH: Mice, Hepatitis B virus, MESH: Hepatitis B Vaccines, MESH: Humans, MESH: Hepatitis B, biology, MESH: Neutralization Tests, MESH: Enzyme-Linked Immunosorbent Assay, virus diseases, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Hepatitis B, medicine.disease, Virology, digestive system diseases, MESH: Hepatitis B Surface Antigens, 3. Good health, Vaccination, MESH: Hepatitis B virus, 030104 developmental biology, MESH: Immunologic Memory, biology.protein, 030211 gastroenterology & hepatology, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Antibody
Abstract: International audience; Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans.
Published: 2020
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8. Fungal mediated innate immune memory, what have we learned?

Author: Jessica Quintin, Immunologie des Infections fongiques - immunology of fungal infections, Institut Pasteur [Paris], Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, This work was supported by the ANR JCJC grant [ANR-16-CE15-0014-01] and the Institut Carnot Pasteur MI grant [ANR 11-CARN 017-01] (to J.Q.)., ANR-16-CE15-0014,IIMory,Mémoire immunologique innée des défenses de l'hôte(2016), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, animal diseases, [SDV]Life Sciences [q-bio], Context (language use), chemical and pharmacologic phenomena, β-glucan, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Fungal Components, Immunological memory, MESH: Monocytes, Monocytes, 03 medical and health sciences, Innate immune memory, 0302 clinical medicine, MESH: Mycoses, Immunity, Candida albicans, Humans, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Immune status, Innate immune system, MESH: Humans, biology, Macrophages, MESH: Candida albicans, Fungi, MESH: Macrophages, Cell Biology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Immunity, Innate, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Mycoses, Immunology, MESH: Immunologic Memory, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Immunologic Memory, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; The binary classification of mammalian immune memory is now obsolete. Innate immune cells carry memory characteristics. The overall capacity of innate immune cells to remember and alter their responses is referred as innate immune memory and the induction of a non-specific memory resulting in an enhanced immune status is termed "trained immunity". Historically, trained immunity was first described as triggered by the human fungal pathogen Candida albicans. Since, numerous studies have accumulated and deciphered the main characteristics of trained immunity mediated by fungi and fungal components. This review aims at presenting the newly described aspect of memory in innate immunity with an emphasis on the historically fungal mediated one, covering the known molecular mechanisms associated with training. In addition, the review uncovers the numerous non-specific effect that β-glucans trigger in the context of infectious diseases and septicaemia, inflammatory diseases and cancer.
Published: 2019
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9. A Seroepidemiological Study of Serogroup A Meningococcal Infection in the African Meningitis Belt

Author: Manigart, Olivier, Trotter, Caroline, Findlow, Helen, Assefa, Abraham, Mihret, Wude, Moti Demisse, Tesfaye, Yeshitela, Biruk, Osei, Isaac, Hodgson, Abraham, Quaye, Stephen Laryea, Sow, Samba, Coulibaly, Mamadou, Diallo, Kanny, Traore, Awa, Collard, Jean-Marc, Moustapha Boukary, Rahamatou, Djermakoye, Oumarou, Mahamane, Ali Elhaji, Jusot, Jean-François, Sokhna, Cheikh, Alavo, Serge, Doucoure, Souleymane, Ba, El Hadj, Dieng, Mariétou, Diallo, Aldiouma, Daugla, Doumagoum Moto, Omotara, Babatunji, Chandramohan, Daniel, Hassan-King, Musa, Nascimento, Maria, Woukeu, Arouna, Borrow, Ray, Stuart, James M, Greenwood, Brian, London School of Hygiene and Tropical Medicine (LSHTM), Medical Research Council Unit The Gambia (MRC), University of Cambridge [UK] (CAM), Public Health England North West [Manchester] (PHE), Public Health England [London], Armauer Hansen Research Institute (AHRI), Navrongo Health Research Centre [Navrongo, Ghana] (NHRC), Centre pour les Vaccins en Développement [Bamako] (CVD), Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Réseau International des Instituts Pasteur (RIIP), Institut de recherche pour le développement (IRD [Sénégal]), Centre de Support en Santé Internationale [N'Djamena, Tchad] (CSSI), University of Maiduguri, This work was supported by Wellcome Trust (grant no. 086546/Z/08/Z), www.wellcome.ac.uk, Bill & Melinda Gates Foundation (grant no. 51251), www.gatesfoundation.org., Trotter, Caroline [0000-0003-4000-2708], and Apollo - University of Cambridge Repository
Subjects: Male, Bacterial Diseases, Physiology, lcsh:Medicine, Meningococcal Disease, Neisseria meningitidis, MESH: Africa, Biochemistry, Ghana, MESH: Meningococcal Vaccines, Geographical Locations, Seroepidemiologic Studies, Infectious Diseases of the Nervous System, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immune Physiology, MESH: Child, MESH: Antibodies, Bacterial, Medicine and Health Sciences, Public and Occupational Health, Enzyme-Linked Immunoassays, lcsh:Science, Child, MESH: Aged, MESH: Immunoglobulin G, Immune System Proteins, MESH: Middle Aged, Vaccination, MESH: Meningitis, Meningococcal, MESH: Enzyme-Linked Immunosorbent Assay, Middle Aged, Antibodies, Bacterial, Vaccination and Immunization, MESH: Infant, Senegal, Infectious Diseases, Neurology, Child, Preschool, Carrier State, MESH: Immunologic Memory, Female, MESH: Carrier State, Research Article, Adult, Adolescent, Inflammatory Diseases, Immunology, Enzyme-Linked Immunosorbent Assay, Meningococcal Vaccines, Meningitis, Meningococcal, Serogroup, Research and Analysis Methods, Antibodies, MESH: Neisseria meningitidis, MESH: Cross-Sectional Studies, Humans, Meningitis, Epidemics, Immunoassays, MESH: Epidemics, Aged, MESH: Adolescent, MESH: Seroepidemiologic Studies, MESH: Humans, lcsh:R, MESH: Child, Preschool, Infant, Biology and Life Sciences, Proteins, MESH: Adult, MESH: Serogroup, MESH: Vaccination, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Cross-Sectional Studies, Immunoglobulin G, People and Places, Africa, Immunologic Techniques, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Ethiopia, Preventive Medicine, Immunologic Memory, MESH: Female
Abstract: International audience; The pattern of epidemic meningococcal disease in the African meningitis belt may be influenced by the background level of population immunity but this has been measured infrequently. A standardised enzyme-linked immunosorbent assay (ELISA) for measuring meningococcal serogroup A IgG antibodies was established at five centres within the meningitis belt. Antibody concentrations were then measured in 3930 individuals stratified by age and residence from six countries. Seroprevalence by age was used in a catalytic model to determine the force of infection. Meningococcal serogroup A IgG antibody concentrations were high in each country but showed heterogeneity across the meningitis belt. The geometric mean concentration (GMC) was highest in Ghana (9.09 μg/mL [95% CI 8.29, 9.97]) and lowest in Ethiopia (1.43 μg/mL [95% CI 1.31, 1.57]) on the margins of the belt. The force of infection was lowest in Ethiopia (λ = 0.028). Variables associated with a concentration above the putative protective level of 2 μg/mL were age, urban residence and a history of recent vaccination with a meningococcal vaccine. Prior to vaccination with the serogroup A meningococcal conjugate vaccine, meningococcal serogroup A IgG antibody concentrations were high across the African meningitis belt and yet the region remained susceptible to epidemics.
Published: 2016
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10. Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

Author: Sylvain Baize, Marion Russier, Stéphanie Reynard, Delphine Pannetier, Vincent Deubel, Alexandra Journeaux, Noël Tordo, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), This work was supported by the Délégation Générale pour l'Armement (0034053). D.P. is a fellow recipient of the Délégation Générale pour l'Armement., Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), and MATEO, MATHIEU
Subjects: CD4-Positive T-Lymphocytes, Enzyme-Linked Immunospot Assay, Cellular immunity, MESH: Flow Cytometry, Lymphocyte Activation, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, Cytotoxic T cell, Lassa fever, Cells, Cultured, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Cytokines, 0303 health sciences, MESH: Dendritic Cells, Reverse Transcriptase Polymerase Chain Reaction, MESH: CD4-Positive T-Lymphocytes, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Lassa virus, MESH: Arenaviruses, Old World, Flow Cytometry, 3. Good health, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, Cytokines, MESH: Cells, Cultured, T cell, Immunology, Enzyme-Linked Immunosorbent Assay, Biology, Microbiology, Virus, MESH: Coculture Techniques, 03 medical and health sciences, MESH: Cell Proliferation, Virology, medicine, Humans, Lassa virus, MESH: Lymphocyte Activation, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cell Proliferation, 030304 developmental biology, MESH: Humans, Arenavirus, Dendritic Cells, Dendritic cell, medicine.disease, biology.organism_classification, Coculture Techniques, Insect Science, Pathogenesis and Immunity, MESH: Enzyme-Linked Immunospot Assay, Arenaviruses, Old World, Immunologic Memory, MESH: T-Lymphocytes, Cytotoxic, T-Lymphocytes, Cytotoxic, 030215 immunology
Abstract: The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (APC) may play a crucial role in controlling infection. Here we developed an in vitro model of dendritic-cell (DC)-T-cell coculture in order to characterize human T-cell responses induced by MV- or LV-infected DCs. Our results show very different responses to infection with LV and MV. MV strongly and durably stimulated CD8 + and CD4 + T cells, showing early and high activation, a strong proliferative response, and acquisition of effector and memory phenotypes. Furthermore, robust and functional CD4 + and CD8 + cytotoxic T lymphocytes (CTL) were generated. LV, however, induced only weak memory responses. Thus, this study allows an improved understanding of the pathogenesis and immune mechanisms involved in the control of human LV.
Published: 2011
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11. Splenic CD8α+ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8+ T-cell memory

Author: Saidi M.Homa Soudja, Grégoire Lauvau, Laura Campisi, Nicolas Glaichenhaus, Frédéric Brau, Anne Lazzari, Frederic Geissmann, Emilie Narni-Mancinelli, Julie Cazareth, Delphine Bassand, Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, and Albert Einstein College of Medicine [New York]
Subjects: MESH: Inflammation, Adoptive cell transfer, MESH: Spleen, Priming (immunology), Cell Count, MESH: T-Lymphocyte Subsets, MESH: Virulence, CD8-Positive T-Lymphocytes, MESH: Listeria monocytogenes, Lymphocyte Activation, MESH: Membrane Transport Proteins, Mice, Cytosol, 0302 clinical medicine, MESH: Cytosol, T-Lymphocyte Subsets, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, Listeriosis, MESH: Bacterial Proteins, Cells, Cultured, Sequence Deletion, Adenosine Triphosphatases, Mice, Inbred BALB C, 0303 health sciences, MESH: Dendritic Cells, Virulence, biology, MESH: Sequence Deletion, Acquired immune system, MESH: CD8-Positive T-Lymphocytes, Adoptive Transfer, 3. Good health, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, MESH: Cells, Cultured, CD8 Antigens, Immunology, MESH: Mice, Inbred BALB C, Inflammation, 03 medical and health sciences, Bacterial Proteins, Antigen, MHC class I, MESH: Adenosine Triphosphatases, medicine, Animals, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, SecA Proteins, MESH: Cell Count, Membrane Transport Proteins, Dendritic Cells, Listeria monocytogenes, MESH: Adoptive Transfer, MESH: Listeriosis, biology.protein, MESH: Antigens, CD8, Immunologic Memory, SEC Translocation Channels, Spleen, CD8, 030215 immunology
Abstract: International audience; Memory CD8(+) T lymphocytes are critical effector cells of the adaptive immune system mediating long-lived pathogen-specific protective immunity. Three signals - antigen, costimulation and inflammation - orchestrate optimal CD8(+) T-cell priming and differentiation into effector and memory cells and shape T-cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α(+) but not the CD8α(-) cDCs most efficiently mediate CD8(+) T-cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I-associated antigens, is most efficient at inducing naïve CD8(+) T-cell differentiation into pathogen-specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α(+) cDCs become endowed with all functional features to optimally prime protective memory CD8(+) T cells in vivo within only a few hours post-immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell-based vaccine therapy.
Published: 2011
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12. Innate or Adaptive Immunity? The Example of Natural Killer Cells

Author: Alessandro Moretta, Wayne M. Yokoyama, Eric Vivier, David H. Raulet, Laurence Zitvogel, Michael A. Caligiuri, Lewis L. Lanier, Sophie Ugolini, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Cancer Research Laboratory [Berkeley] (CRI), University of California [Berkeley], University of California-University of California, Dipartimento di Medicina Sperimentale, Universita degli studi di Genova, Comprehensive Cancer Center, Ohio State University [Columbus] (OSU), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Medicine, Université Paris-Sud - Paris 11 (UP11), University of California SF (UNIVERSITY OF CALIFORNIA), University of California, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Università degli studi di Genova = University of Genoa (UniGe), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of California (UC)
Subjects: MESH: Killer Cells, Natural, Adaptive Immunity, Biology, Article, Natural killer cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Neoplasms, medicine, Animals, Humans, MESH: Animals, MESH: Neoplasms, Receptors, Immunologic, Receptor, MESH: Receptors, Immunologic, 030304 developmental biology, 0303 health sciences, MESH: Humans, Multidisciplinary, Innate immune system, Effector, Innate lymphoid cell, Acquired immune system, Immunity, Innate, Killer Cells, Natural, MESH: Virus Diseases, Self Tolerance, medicine.anatomical_structure, Virus Diseases, MESH: Self Tolerance, Immunology, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Immunologic Memory, Neuroscience, MESH: Adaptive Immunity, 030215 immunology
Abstract: International audience; Natural killer (NK) cells were originally defined as effector lymphocytes of innate immunity endowed with constitutive cytolytic functions. More recently, a more nuanced view of NK cells has emerged. NK cells are now recognized to express a repertoire of activating and inhibitory receptors that is calibrated to ensure self-tolerance while allowing efficacy against assaults such as viral infection and tumor development. Moreover, NK cells do not react in an invariant manner but rather adapt to their environment. Finally, recent studies have unveiled that NK cells can also mount a form of antigen-specific immunologic memory. NK cells thus exert sophisticated biological functions that are attributes of both innate and adaptive immunity, blurring the functional borders between these two arms of the immune response.
Published: 2011
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13. TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal

Author: Anne Cottalorda, Charles-Antoine Coupet, Blandine C. Mercier, Jacqueline Marvel, Nathalie Bonnefoy-Berard, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fargeot, Alexandra
Subjects: Adoptive cell transfer, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Blotting, Western, Immunology, Receptors, Antigen, T-Cell, Mice, Transgenic, MESH: Flow Cytometry, CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, Mice, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Antigen, Animals, MESH: Blotting, Western, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, 0303 health sciences, Innate immune system, T-cell receptor, MESH: Toll-Like Receptor 2, MESH: Receptors, Antigen, T-Cell, MESH: 1-Phosphatidylinositol 3-Kinase, Flow Cytometry, Acquired immune system, Adoptive Transfer, MESH: CD8-Positive T-Lymphocytes, Toll-Like Receptor 2, Cell biology, MESH: Adoptive Transfer, TLR2, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic Memory, 030215 immunology
Abstract: TLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal.
Published: 2009
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14. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

Author: Maria Mamani-Matsuda, Frédéric Gauthier, Claude-Agnès Reynaud, Corinne Cordier, Capucine Picard, Damiana Lecoeuche, Jean-Claude Weill, Sandra K. Weller, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ligue Nationale contre le Cancer, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, and Weller, Sandra
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH: Immunoglobulin Variable Region, Immunoglobulin D, MESH: Variation (Genetics), 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Variable Region, MESH: Antigens, CD, 0303 health sciences, biology, MESH : Variation (Genetics), MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Articles, MESH: Infant, MESH: Immunoglobulin M, somatic hypermutation, "somatic hypermutation", MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: B-Lymphocyte Subsets, MESH : Spleen, MESH: Immunoglobulin mu-Chains, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Immunologic Memory, MESH: Gene Rearrangement, MESH : Immunoglobulin M, Immunology, Somatic hypermutation, "splenic marginal zone", chemical and pharmacologic phenomena, MESH : Immunoglobulin D, Article, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, Antigen, MESH : Antigens, CD27, MESH: B-Lymphocytes, MESH : Antigens, CD, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, MESH: Transcription, Genetic, MESH : Humans, Ig repertoire, Germinal center, MESH : Transcription, Genetic, Gene rearrangement, MESH : Gene Rearrangement, splenic marginal zone, B-1 cell, MESH: T-Lymphocytes, MESH : Immunoglobulin mu-Chains, Immunoglobulin M, biology.protein, 030215 immunology, MESH : B-Lymphocyte Subsets, "Ig repertoire"
Abstract: International audience; T cell-dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell-independent responses. We used this dissociation to analyze the repertoire diversification of IgM(+)IgD(+)CD27(+) B cells (also known as "IgM memory" B cells), comparing these cells with switched B cells in children
Published: 2008
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15. A subset of functional effector-memory CD8+T lymphocytes in human immunodeficiency virus-infected patients

Author: Jean-Marie Estavoyer, Audrey Varin, Georges Herbein, Anne-Zélie Decrion, Christine Drobacheff, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: MESH: Antigens, CD28, viruses, HIV Infections, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Interleukin 21, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Cells, Cultured, 0303 health sciences, virus diseases, CD28, Cell Differentiation, hemic and immune systems, MESH: HIV Infections, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Interferon-gamma, Immunology, chemical and pharmacologic phenomena, Biology, Interferon-gamma, 03 medical and health sciences, CD28 Antigens, Antigen, MESH: Cell Proliferation, Humans, MESH: Lymphocyte Activation, Antigen-presenting cell, Cell Proliferation, 030304 developmental biology, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Chronic Disease, Original Articles, Virology, MESH: Tumor Necrosis Factor-alpha, Peripheral blood lymphocyte, Chronic Disease, Immunologic Memory, 030215 immunology
Abstract: International audience; CD8(+) T cells provide protective immune responses via both cytolytic and non-cytolytic mechanisms in subjects infected with human immunodeficiency virus (HIV). In the present study, we investigated the CD28 expression of CD8(+) T cells present in the peripheral blood lymphocyte subset isolated from chronically HIV-infected subjects. Using flow cytometric analysis, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28-negative, intermediate (int) and high, was seen for CD8(+) T cells. Our study focused mostly on the CD28(int) CD8(+) T cells. The CD28(int) CD8(+) T cells are CD57(-) CD27(+) CD45RO(+) CD45RA(-) CCR7(low) CD62L(int). The proliferative capacity of CD28(int) CD8(+) T cells was intermediate between those of CD28(-) CD8(+) T cells and CD28(high) CD8(+) T cells. The CD28(int) CD8(+) T cells are specific for HIV, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) antigens as measured by human leucocyte antigen pentamer binding and produce both intracellular interferon-gamma and tumour necrosis factor-alpha in response to their cognate viral peptides. The CD28(int) CD8(+) T cells have HIV-specific, CMV-specific and EBV-specific cytotoxic activity in response to their cognate viral peptides. These findings indicate that a subset of functional effector-memory CD8(+) T cells specific for HIV, CMV and EBV antigens may contribute to an efficient immune response in HIV-infected subjects.
Published: 2007
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16. In HIV-1 pathogenesis the die is cast during primary infection

Author: Ben Berkhout, Simon Wain-Hobson, Mireille Centlivre, Monica Sala, Rétrovirologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: CD4-Positive T-Lymphocytes, Lymphoid Tissue, medicine.medical_treatment, Immunology, HIV Infections, Biology, Virus Replication, Virus, MESH: HIV-1, Pathogenesis, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), medicine, Animals, Humans, Immunology and Allergy, MESH: Animals, 030304 developmental biology, 0303 health sciences, MESH: Humans, 030306 microbiology, MESH: Virus Replication, MESH: CD4-Positive T-Lymphocytes, MESH: HIV Infections, Immunotherapy, biology.organism_classification, medicine.disease, Virology, 3. Good health, Intestines, Infectious Diseases, Lymphatic system, Viral replication, Acute Disease, MESH: Lymphoid Tissue, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Lentivirus, HIV-1, MESH: Immunologic Memory, MESH: Acute Disease, Viral disease, Immunologic Memory, MESH: Intestines
Abstract: The chronic stage of HIV-1 infection has been extensively described as a slowly evolving phase, in which the virus induces T-cell death slightly faster than the human body is able to recover. In contrast, T-cell and viral replication dynamics during primary infection have been less well studied. Recent studies in the SIV-macaque model and in HIV-positive patients during the acute infection period have highlighted the massive and irreversible depletion of CD4 memory T cells in the mucosa, particularly in the gut. Hence, gut-associated lymphoid tissue (GALT) plays a central role in the early stages of HIV-1 pathogenesis. Due to its particular cytokine expression pattern, GALT may favour the differential replication of certain HIV-1 subtypes during primary infection, particularly of subtype C. This could enhance the chance of a successful transmission. Moreover, these early events taking place in GALT during primary infection have major implications for therapy and vaccine design. (c) 2007 Lippincott Williams & Wilkins
Published: 2007
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17. IL-2 and IL-15 regulate CD8+ memory T-cell differentiation but are dispensable for protective recall responses

Author: Mathieu, Cédric, Beltra, Jean-Christophe, Charpentier, Tania, Bourbonnais, Sara, Di Santo, James P, Lamarre, Alain, Decaluwe, Hélène, Research Center, CHU Sainte-Justine, Universite de Montreal, Montreal, Quebec, Canada, Centre de recherche de l'hôpital Sainte Justine, CHU Sainte Justine [Montréal]-CHU Sainte Justine [Montréal], University of Montréal, University of Montreal, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Funded by - Canadian Institutes of Health Research. Grant Number: CIHR MOP-130469 - Institut Pasteur and the INSERM, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Interleukin-15, MESH: Cell Differentiation, IL-2, [SDV]Life Sciences [q-bio], MESH: Interleukin-15, Cell Differentiation, T-cell differentiation, MESH: Interleukin-2, CD8-Positive T-Lymphocytes, CD8+ T cells, MESH: CD8-Positive T-Lymphocytes, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, MESH: Interleukin-2 Receptor beta Subunit, Mice, IL-15, Memory, MESH: Mice, Inbred C57BL, MESH: Immunologic Memory, Animals, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, Immunologic Memory, MESH: Mice
Abstract: International audience; The ability to mount effective secondary responses is a cardinal feature of memory CD8(+) T cells. An understanding of the factors that regulate the generation and recall capacities of memory T cells remains to be ascertained. Several cues indicate that two highly related cytokines, IL-2 and IL-15, share redundant functions in this process. To establish their combined roles in memory CD8(+) T-cell development, maintenance, and secondary responses, we compared the outcome of adoptively transferred IL2Rβ(+/-) or IL2Rβ(-/-) CD8(+) T cells after an acute viral infection in mice. Our results demonstrate that both IL-2 and IL-15 signals condition the differentiation of primary and secondary short-lived effector cells by altering the transcriptional network governing lineage choices. These two cytokines also regulate the homeostasis of the memory T-cell pool, with effector memory CD8(+) T cells being the most sensitive to these two interleukins. Noticeably, the inability to respond to both cytokines limits the proliferation and survival of primary and secondary effectors cells, whereas it does not preclude potent cytotoxic functions and viral control either initially or upon rechallenge. Globally, these results indicate that lack of IL-2 and IL-15 signaling modulates the CD8(+) T-cell differentiation program but does not impede adequate effector functions.
Published: 2015
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18. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

Author: Lionel Le Bourhis, Olivier Lantz, Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Sylvie Rabot, Alexandra Kachaner, Emmanuel Martin, Claire Soudais, Stanislas Mondot, Virginie Premel, Livine Duban, Jean Jaubert, Molly A. Ingersoll, Jean-Pierre de Villartay, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biopathologie, Institut Curie [Paris], This work was supported by grants from INSERM, Agence Nationale de la Recherche (ANR), DIM Ile de France, Association pour la Recherche sur la Sclérose En Plaques (ARSEP), Institut Mérieux, and Institut Curie. Y.K. Mburu is a recipient of the Lloyd J. Old Memorial Award and is supported by an Irvington Institute postdoctoral fellowship from the Cancer Research Institute., Vougny, Marie-Christine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie
Subjects: MESH: Minor Histocompatibility Antigens, MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, Receptors, Antigen, T-Cell, alpha-beta, MESH: Chemotaxis, Leukocyte, MESH: Urinary Tract Infections, Lymphocyte Activation, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, MESH: Promyelocytic Leukemia Zinc Finger Protein, Mice, 0302 clinical medicine, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Mice, Knockout, 0303 health sciences, education.field_of_study, Lymphokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, Microbiota, MESH: Polymorphism, Single Nucleotide, General Medicine, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH: Crosses, Genetic, Chemotaxis, Leukocyte, medicine.anatomical_structure, Phenotype, Radiation Chimera, Urinary Tract Infections, MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Kruppel-Like Transcription Factors, Research Article, MESH: Lymphocyte Count, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoid Tissue, MESH: Radiation Chimera, MESH: Mice, Transgenic, T cell, Population, Congenic, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Biology, MESH: Phenotype, Polymorphism, Single Nucleotide, Minor Histocompatibility Antigens, 03 medical and health sciences, Mice, Congenic, MESH: Mice, Congenic, MESH: Mice, Inbred C57BL, MESH: Germ-Free Life, medicine, Animals, Germ-Free Life, Humans, MESH: Microbiota, Lymphocyte Count, Receptors, Cytokine, education, MESH: Lymphocyte Activation, MESH: Mice, Crosses, Genetic, 030304 developmental biology, MESH: Humans, MESH: Lymphokines, T-cell receptor, Histocompatibility Antigens Class I, Laboratory mouse, Gene rearrangement, Molecular biology, MESH: Receptors, Cytokine, Mice, Inbred C57BL, Disease Models, Animal, MESH: Natural Killer T-Cells, MESH: Lymphoid Tissue, Natural Killer T-Cells, MESH: Disease Models, Animal, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Immunologic Memory, MESH: Female, 030215 immunology
Abstract: Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-alpha chain and restricting molecule MR1, this population is rare in laboratory mouse strains (approximate to 0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-alpha locus and led to higher usage of the distal V alpha segments, including V alpha 19. We generated a MAIT(hl) congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44(+)) CD4(-)CD8(lo/neg) T cells with tissue-homing properties (CCR6*CCR7(-)). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18R alpha, and IL-12R beta and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptory gamma (R0R gamma t). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIT(hi) congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.
Published: 2015
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19. Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesis

Author: Claudine Schiff, Bertrand Montpellier, Julie Agopian, Bertrand Nadel, Michèle Milili, Sandrine Roulland, Pierre Grenot, Pascal Gauduchon, Jean Navarro, Pierre Lebailly, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Follicular lymphoma, Chromosomal translocation, Biochemistry, Immunoglobulin D, Translocation, Genetic, Pathogenesis, MESH: Lymphoma, Follicular, 0302 clinical medicine, Immunology and Allergy, Memory B cell, Lymphoma, Follicular, 0303 health sciences, education.field_of_study, biology, MESH: G0 Phase, Hematology, MESH: Translocation, Genetic, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, MESH: Immunologic Memory, Biomarker (medicine), [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: B-Lymphocyte Subsets, Naive B cell, Immunology, Population, B-Lymphocyte Subsets, Somatic hypermutation, Resting Phase, Cell Cycle, 03 medical and health sciences, medicine, Humans, education, 030304 developmental biology, Chromosomes, Human, Pair 14, MESH: Humans, MESH: Clone Cells, Brief Definitive Report, Germinal center, Cell Biology, medicine.disease, Molecular biology, Lymphoma, Clone Cells, Immunoglobulin M, MESH: Cell Transformation, Neoplastic, biology.protein, MESH: Chromosomes, Human, Pair 14, Brief Definitive Reports, MESH: Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 18, Immunologic Memory
Abstract: Follicular lymphoma (FL) is one of the most common B-cell lymphoma, and remains virtually incurable despite its relatively indolent nature. T(14;18)(q32;q21), the genetic hallmark and early initiating event of FL pathogenesis, is also present at low frequency (10−5–10−7) in blood from healthy individuals (HI), indicating that t(14;18) and the ensuing BCL2 overexpression is necessary but not sufficient for malignant transformation. It has long been assumed that in HI, t(14;18) is carried by circulating quiescent naïve B-cells, where its oncogenic potential would be restrained. Yet, several reports, including long-term persistence and immunomodulation of t(14;18)+ cells in lymphoma-free individuals, led us to question this model and investigate the status of circulating t(14;18)+ cells in HI. We first determined if t(14;18)+ cells are naïve B-cells by assessing class-switch recombination (CSR) on the translocated allele. Using 2 long-range PCR assays designed to amplify unswitched BCL2/Sμ and switched BCL2/Sg regions, DNA samples from 6 HI with t(14;18) were tested. Contrary to previous assumptions, our data clearly show that most peripheral t(14;18)+ cells already underwent CSR (n=5/6) and therefore that most t(14;18)+ cells are not naïve B-cells. Are they then memory B cells? Naïve and memory B cell subsets from 9 HI were isolated by cell sorting according to IgD and CD27 markers, and the rate of t(14;18) analyzed in each subset relatively to that of the total B cells. Strikingly, while the level of naïve t(14;18)+ cells remained at baseline for all individuals, memory B-cells tightly accounted for the wide modulation of t(14;18) frequencies observed between individuals. In addition, sequence analysis of t(14;18) clones revealed that this wide modulation was not due to the accumulation of clonally unrelated t(14;18) naïve B-cells, but rather to the clonal expansion of t(14;18)-bearing memory B-cells. To further define the t(14;18)+ cells, we next examined the repartition of the translocation in the IgD−/CD27+ and IgD+/CD27+ memory B-cell subsets. Unexpectedly, we found that the IgD+/CD27+ subset contained significantly higher rates of translocation than the IgD−/CD27+, both in terms of prevalence and frequency. Thus, while CSR is found in the majority of translocated alleles (~75%), most t(14;18)+ memory B cells have not switched their productive allele (~70%) and express an IgM/D. Most importantly, although atypical among physiological peripheral B-cells, this “allelic paradox” is a specific hallmark of FL, and suggests the presence of the same selective pressure in favor of sIgM expression on a B-cell population that is at the same time permanently driven to switch. In line with B-cell hyperplasia in BCL2 transgenic mice slowly progressing to low grade lymphoma, it is likely that “FL-like” cells in HI are rescued by BCL2 from apoptosis, and “frozen” at a differentiation stage in which constitutive AID expression drives continuous somatic hypermutation and CSR activity, two mechanisms conferring a high propensity for genomic instability. Altogether, our findings identify a novel intermediate step in early lymphomagenesis, and strongly impact both on the current understanding of disease progression from potent pre-malignant niches, and on the proper handling of t(14;18) frequency in blood as a potential early biomarker for lymphoma.
Published: 2006
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20. DNA Polymerase η Is Involved in Hypermutation Occurring during Immunoglobulin Class Switch Recombination

Author: Sandra Weller, Anne Stary, Claude-Agnès Reynaud, Alain Sarasin, Jean-Claude Weill, Said Aoufouchi, Ahmad Faili, Françoise Vuillier, Ribierre, Hélène, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immuno-Hématologie et Immunopathologie, Institut Pasteur [Paris] (IP), Etude des relations instabilité génétique et cancer (ERIGC), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Introns, DNA polymerase, DNA Mutational Analysis, DNA-Directed DNA Polymerase, MESH: Base Sequence, Gene mutation, Cytosine Deaminase, translesional DNA polymerases, 0302 clinical medicine, MESH: DNA-Directed DNA Polymerase, Immunology and Allergy, somatic mutation, MESH: DNA Mutational Analysis, Polymerase, Recombination, Genetic, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, B-Lymphocytes, 0303 health sciences, MESH: Middle Aged, biology, MESH: DNA, Cytidine deaminase, Middle Aged, MESH: Immunoglobulin Class Switching, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, Female, MESH: Recombination, Genetic, Adult, MESH: DNA Primers, MESH: Somatic Hypermutation, Immunoglobulin, Molecular Sequence Data, Immunology, xeroderma pigmentosum variant syndrome, Somatic hypermutation, Article, Immunoglobulin Class Switch Recombination, 03 medical and health sciences, Tandem repeat, Cytidine Deaminase, MESH: B-Lymphocytes, Humans, DNA Primers, MESH: Xeroderma Pigmentosum, MESH: Cytidine Deaminase, 030304 developmental biology, Xeroderma Pigmentosum, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH: Cytosine Deaminase, MESH: Adult, DNA, Immunoglobulin Class Switching, Molecular biology, Introns, Immunoglobulin class switching, pol η, biology.protein, Somatic Hypermutation, Immunoglobulin, Immunologic Memory, MESH: Female, 030215 immunology
Abstract: Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase η (pol η), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol η is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.
Published: 2004
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21. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Author: Cisca Wijmenga, Mihai G. Netea, Hendrik G. Stunnenberg, Ali Aghajanirefah, Nagesha A.S. Rao, Frances Burden, Aylwin Ng, Kim Berentsen, Sadia Saeed, Jacqueline M. Ratter, Hindrik H. D. Kerstens, Jessica Quintin, Menno ter Huurne, Amit Mandoli, Nilofar Sharifi, Kate Downes, Tom van Schaik, Willem H. Ouwehand, Martijn van der Ent, Colin Logie, Ramnik J. Xavier, Shih-Chin Cheng, Filomena Matarese, Joost H.A. Martens, Evangelos J. Giamarellos-Bourboulis, Leo A. B. Joosten, Eva M. Janssen-Megens, Mattia Frontini, Vinod Kumar, Jos W. M. van der Meer, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Radboud university [Nijmegen], Radboud University Medical Center [Nijmegen], Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Cambridge [UK] (CAM), University of Groningen [Groningen], National and Kapodistrian University of Athens (NKUA), and Massachusetts Institute of Technology (MIT)
Subjects: MESH: Cell Differentiation, LIVER X RECEPTOR, REGULATORY ELEMENTS, [SDV]Life Sciences [q-bio], Secondary infection, NF-KAPPA-B, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Biology, MESH: Monocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, DENDRITIC CELLS, 03 medical and health sciences, MESH: Inflammasomes, 0302 clinical medicine, HOST-DEFENSE, INFLAMMATION, Immunity, medicine, IRAK-M, HUMAN GENOME, MESH: Animals, MESH: Epigenesis, Genetic, Epigenetics, Molecular Biology, MESH: Mice, Transcription factor, 030304 developmental biology, GENE-EXPRESSION, 0303 health sciences, MESH: Humans, Multidisciplinary, Innate immune system, MESH: beta-Glucans, Monocyte, MESH: Macrophages, Inflammasome, MESH: Transcription Factors, MESH: Deoxyribonuclease I, MESH: Genomic Imprinting, TRANSCRIPTION FACTORS, medicine.anatomical_structure, MESH: Binding Sites, 030220 oncology & carcinogenesis, Monocyte differentiation, Immunology, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, medicine.drug
Abstract: A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducing immune responses, Saeed et al. document the epigenetic changes in the genome that underlie immune cell differentiation. Cheng et al. demonstrate that trained monocytes are highly dependent on the breakdown of sugars in the presence of oxygen, which allows cells to produce the energy needed to mount an immune response. Chen et al. examine RNA transcripts and find that specific cell lineages use RNA transcripts of different length and composition (isoforms) to form proteins. Together, the studies reveal how epigenetic effects can drive the development of blood cells involved in the immune system. Science , this issue 10.1126/science.1251086 , 10.1126/science.1250684 , 10.1126/science.1251033
Published: 2014
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22. mTOR- and HIF-1 alpha-mediated aerobic glycolysis as metabolic basis for trained immunity

Author: Shih-Chin Cheng, Peter M.T. Deen, Hendrik G. Stunnenberg, Joost H.A. Martens, Jessica Quintin, Robert A. Cramer, Kelly M. Shepardson, Sadia Saeed, Rob J.W. Arts, Nagesha Appukudige Rao, Brian M. J. W. van der Veer, Cisca Wijmenga, Yang Li, Colin Logie, Frank L. van de Veerdonk, Ramnik J. Xavier, Ganesh R. Manjeri, Vinod Kumar, Jos W. M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Daniela C. Ifrim, Mihai G. Netea, Luke A. J. O'Neill, Leo A. B. Joosten, Peter H.G.M. Willems, Ali Aghajanirefah, Aylwin Ng, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Radboud University Medical Center [Nijmegen], Geisel School of Medicine at Dartmouth, Radboud university [Nijmegen], University Medical Center Groningen [Groningen] (UMCG), National and Kapodistrian University of Athens (NKUA), Trinity College Dublin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), and Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]
Subjects: Male, beta-Glucans, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], MESH: Monocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Monocytes, Epigenesis, Genetic, ACTIVATION, Mice, 0302 clinical medicine, Candida albicans, INFECTION, MESH: Staphylococcus aureus, Glycolysis, MESH: Animals, MESH: Epigenesis, Genetic, PROTECTION, MACROPHAGES, MESH: Sepsis, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, Multidisciplinary, MESH: beta-Glucans, TOR Serine-Threonine Kinases, Candidiasis, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Staphylococcal Infections, Aerobiosis, MESH: Candidiasis, Cell biology, MESH: Glucose, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, 030220 oncology & carcinogenesis, MESH: Glycolysis, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunity, Innate, BETA-GLUCAN, EXPRESSION, Staphylococcus aureus, Secondary infection, MESH: Staphylococcal Infections, Biology, Article, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, 03 medical and health sciences, INFLAMMATION, Immunity, MESH: Mice, Inbred C57BL, Sepsis, MESH: Aerobiosis, Animals, Humans, REINFECTION, Protein kinase B, MESH: Mice, PI3K/AKT/mTOR pathway, MESH: TOR Serine-Threonine Kinases, 030304 developmental biology, Innate immune system, MESH: Humans, MESH: Candida albicans, MESH: Transcriptome, Hypoxia-Inducible Factor 1, alpha Subunit, Immunity, Innate, MESH: Male, Mice, Inbred C57BL, Disease Models, Animal, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Glucose, Anaerobic glycolysis, CELLS, INNATE IMMUNITY, NAD+ kinase, MESH: Disease Models, Animal, Transcriptome, Immunologic Memory, MESH: Female
Abstract: A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducing immune responses, Saeed et al. document the epigenetic changes in the genome that underlie immune cell differentiation. Cheng et al. demonstrate that trained monocytes are highly dependent on the breakdown of sugars in the presence of oxygen, which allows cells to produce the energy needed to mount an immune response. Chen et al. examine RNA transcripts and find that specific cell lineages use RNA transcripts of different length and composition (isoforms) to form proteins. Together, the studies reveal how epigenetic effects can drive the development of blood cells involved in the immune system. Science , this issue 10.1126/science.1251086 , 10.1126/science.1250684 , 10.1126/science.1251033
Published: 2014
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23. Innate immune memory: towards a better understanding of host defense mechanisms

Author: Jessica Quintin, Shih-Chin Cheng, Jos W. M. van der Meer, Mihai G. Netea, and Radboud University Medical Center [Nijmegen]
Subjects: MESH: Killer Cells, Natural, T-Lymphocytes, Secondary infection, [SDV]Life Sciences [q-bio], animal diseases, Immunology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], chemical and pharmacologic phenomena, Adaptive Immunity, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Classical complement pathway, Immunity, MESH: B-Lymphocytes, Animals, Humans, Immunology and Allergy, MESH: Animals, Epigenetics, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, B-Lymphocytes, Innate immune system, MESH: Humans, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Innate lymphoid cell, biochemical phenomena, metabolism, and nutrition, Acquired immune system, Immunity, Innate, Killer Cells, Natural, Histone, MESH: T-Lymphocytes, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, biology.protein, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, bacteria, MESH: Immunity, Innate, Immunologic Memory, MESH: Adaptive Immunity
Abstract: Item does not contain fulltext Innate immunity is classically defined as unable to build up immunological memory. Recently however, the assumption of the lack of immunological memory within innate immune responses has been reconsidered. Plants and invertebrates lacking adaptive immune system can be protected against secondary infections. It has been shown that mammals can build cross-protection to secondary infections independently of T-lymphocytes and B-lymphocytes. Moreover, recent studies have demonstrated that innate immune cells such as NK cells and monocytes can display adaptive characteristics, a novel concept for which the term trained immunity has been proposed. Several mechanisms are involved in mediating innate immune memory, among which epigenetic histone modifications and modulation of recognition receptors on the surface of innate immune cells are likely to play a central role.
Published: 2014
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24. Differential CD4-dependent inhibition of JNK but not Erk-2 activities in human naive and memory CD4+ T cell populations

Author: Annalck Pallier, Sébastien Jauliac, Claire Hivroz, Alain Fischer, Nada Jabado, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Jauliac, Sebastien
Subjects: CD4-Positive T-Lymphocytes, MESH: Mitogen-Activated Protein, MAPK/ERK pathway, MESH: Enzyme Activation, Naive T cell, MAP Kinase Kinase 4, CD3, T cell, Immunology, Naive B cell, MESH: Antigens, CD4, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, MESH: Antibodies, Monoclonal, [SDV.CAN] Life Sciences [q-bio]/Cancer, Aldesleukin, medicine, Humans, Immunology and Allergy, MESH: Ionophores, Protein Kinase Inhibitors, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase Kinases, MESH: Humans, Ionophores, biology, JNK Mitogen-Activated Protein Kinases, Antibodies, Monoclonal, MESH: CD4-Positive T-Lymphocytes, CD28, MESH: Ca(2+)-Calmodulin Dependent Protein Kinase, MESH: JNK Mitogen-Activated Protein Kinases, General Medicine, T lymphocyte, Cell biology, Enzyme Activation, medicine.anatomical_structure, CD4 Antigens, Calcium-Calmodulin-Dependent Protein Kinases, MESH: Immunologic Memory, biology.protein, Tetradecanoylphorbol Acetate, Immunologic Memory, MESH: MAP Kinase Kinase 4
Abstract: CD4 ligand binding to the CD4 molecules has been shown to inhibit T cell proliferation and IL-2 transcription and synthesis. We have recently shown that this inhibition correlated with a CD4-mediated inhibition of the kinase Erk-2 and c-Jun-N-terminal kinases (JNK) which play a key role in IL-2 transcription. Moreover, we have previously reported that antigen-independent adhesion of CD45RObright/CD4+ T cells to B cells is negatively regulated by CD4 ligands, whereas that of CD45RAbright/CD4+ naive T cells is not. Other groups have described, in murine models, a differential sensitivity of memory and naive T cells to CD4-mediated inhibitory effects on T cell activation. The aim of the present report was to study the sensitivity of the naive and memory CD4+ T cell populations to the CD4-mediated inhibition of Erk-2 and JNK activation. Our data show that preincubation with anti-CD4 mAb, of the CD45RAbright/CD4+ naive and the CD45RObright/CD4+ memory human T cell populations, induces inhibition of both Erk-2 phosphorylation and Erk-2 activation by phorbol ester or anti-CD3 mAb. In contrast, CD3 mediated JNK activation was inhibited in the memory but not in the naive CD4+ T cell population, whereas JNK activation by phorbol ester or phorbol esters plus Ca2+ ionophore was inhibited by anti-CD4 mAb in both T cell populations. These data further demonstrate a differential sensitivity of naive and memory CD4+ T cell populations to the CD4-mediated negative signaling.
Published: 1998
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25. IL-15 inhibits IL-7Rα expression by memory-phenotype CD8⁺ T cells in the bone marrow

Author: Angela C, Quinci, Sara, Vitale, Elisabetta, Parretta, Alessandra, Soriani, Maria L, Iannitto, Marco, Cippitelli, Cinzia, Fionda, Silvia, Bulfone-Paus, Angela, Santoni, Francesca, Di Rosa, Department of Molecular Medicine, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany, CNR - National Research Council of Italy, and Institute of Molecular Biology and Pathology
Subjects: chain cytokines, t-cell homeostasis, t-cell memory, t-cell recirculation, γ-chain cytokines, MESH: Receptors, Interleukin-7, MESH: Mice, Transgenic, MESH: Spleen, MESH: Interleukin-15, Down-Regulation, Mice, Transgenic, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, MESH: Antigens, CD44, MESH: Down-Regulation, Mice, Bone Marrow, MESH: Mice, Inbred C57BL, MESH: Forkhead Transcription Factors, MESH: Promoter Regions, Genetic, Animals, MESH: Animals, Promoter Regions, Genetic, MESH: Mice, Interleukin-15, Receptors, Interleukin-7, Forkhead Box Protein O1, virus diseases, Forkhead Transcription Factors, hemic and immune systems, MESH: CD8-Positive T-Lymphocytes, Mice, Inbred C57BL, Hyaluronan Receptors, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Bone Marrow, Immunologic Memory, MESH: Female, Spleen
Abstract: International audience; CD127 is the IL-7 receptor α-chain and its expression is tightly regulated during T-cell differentiation. We previously showed that the bone marrow (BM) is a key organ for proliferation and maintenance of both antigen-specific and CD44(high) memory CD8(+) T cells. Interestingly, BM memory CD8(+) T cells express lower levels of membrane CD127 than do the corresponding spleen and lymph node cells. We investigated the requirements for CD127 downmodulation by CD44(high) memory-phenotype CD8(+) T cells in the BM of C57BL/6 mice. By comparing genetically modified (i.e. CD127tg, IL-7 KO, IL-15 KO, IL-15Rα KO) with wild-type (WT) mice, we found that the key molecule regulating CD127 downmodulation was IL-15 but not IL-7, and that the intact CD127 gene was required, including the promoter. Indeed, CD127 mRNA transcript levels were lower in CD44(high) CD8(+) T cells from the BM than in those from the spleen of WT mice, indicating organ-specific regulation. Although levels of the CD127 transactivator Foxo1 were low in BM CD44(high) CD8(+) T cells, Foxo1 was not involved in IL-15-induced CD127 downmodulation. Thus, recirculating CD44(high) CD8(+) T cells passing through the BM transiently downregulate CD127 in response to IL-15, with implications for human therapies acting on the IL-7/CD127 axis, for example cytokine treatments in cancer patients.
Published: 2012
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26. Tuning of natural killer cell reactivity by NKp46 and Helios calibrates T cell responses

Author: Bruce Beutler, Marta Gut, Sam Kung, Bernard Malissen, Claire Bernat, Simon Heath, Marie Malissen, Eric Vivier, Jordi Estellé, Frédéric Vély, Aude De Gassart, Louis Noël Gastinel, Emilie Narni-Mancinelli, Aurore Fenis, Sophie Ugolini, Baptiste N. Jaeger, Elodie Bertosio, Sajid Mahmood, Ivo Gut, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11), University of Manitoba [Winnipeg], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centro Nacional de Análisi Genómico (CNAG), Centro Nacional de Análisis Genómico, Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology and Microbial Science, The Scripps Research Institute [La Jolla, San Diego], Centre Nacional D'Anàlisi Genómica, Parc Cientific de Barcelona, Apotex Center - University of Manitoba, Haon, Marie Laure, Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Scripps Research Institute, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Muromegalovirus, Transcription, Genetic, T-Lymphocytes, Cell, Mutant, MESH: Herpesviridae Infections, Adaptive Immunity, CD8-Positive T-Lymphocytes, medicine.disease_cause, MESH: Down-Regulation, MESH: Antibodies, Monoclonal, Mice, 0302 clinical medicine, Antigens, Ly, MESH: Animals, Listeriosis, MESH: Mutagenesis, 0303 health sciences, Mutation, MESH: Genetic Complementation Test, Multidisciplinary, Antibodies, Monoclonal, MESH: Antigens, Ly, MESH: Transcription Factors, Herpesviridae Infections, Viral Load, MESH: Amino Acid Substitution, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Cell biology, DNA-Binding Proteins, Killer Cells, Natural, medicine.anatomical_structure, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Viral Load, MESH: Killer Cells, Natural, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, T cell, MESH: Natural Cytotoxicity Triggering Receptor 1, MESH: Muromegalovirus, Down-Regulation, Mice, Transgenic, Biology, Natural killer cell, Cell Line, 03 medical and health sciences, Immune system, MESH: Mice, Inbred C57BL, MESH: Antibodies, Blocking, medicine, Gene silencing, Animals, Antibodies, Blocking, Transcription factor, MESH: Mice, 030304 developmental biology, Natural Cytotoxicity Triggering Receptor 1, MESH: Transcription, Genetic, Genetic Complementation Test, MESH: Cell Line, Mice, Inbred C57BL, MESH: T-Lymphocytes, Amino Acid Substitution, MESH: Listeriosis, Mutagenesis, Immunology, Immunologic Memory, MESH: Adaptive Immunity, MESH: DNA-Binding Proteins, 030215 immunology, Transcription Factors
Abstract: Natural Killer Controls Cytolytic natural killer (NK) cells participate in both antimicrobial and antitumor immunity. Their responsiveness is tuned through signals received through a variety of inhibitory and activating receptors expressed on their cell surface. Narni-Mancinelli et al. (p. 344 ) now show that signaling through the activating receptor NKp46 paradoxically keeps NK cell responses in check. NK cells from mice with disrupted NKp46 expression were hyperresponsive to stimulation and better protected against viral infection. NK cell responses, which are part of the early response to infection, may thus need to be carefully tuned to ensure optimal initiation of adaptive immunity and formation of protective long-lived memory cells.
Published: 2012
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27. Identification of pluripotent and adult stem cell genes unrelated to cell cycle and associated with poor prognosis in multiple myeloma

Author: Hartmut Goldschmidt, Jean François Rossi, Alboukadel Kassambara, Bernard Klein, Dirk Hose, Thierry Rème, Jennifer Torrent, Jérôme Moreaux, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Association pour la Recherche sur le Cancer, ARC (SL220110603450, Paris, France), The Tumorzentrum Heidelberg/Mannheim, Germany, The Deutsche Krebshilfe, Bonn, Germany, The Deutsche Forschungsgemeinschaft (Transregio TRR79), Bonn, Germany, Frei, Monique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Genetic Screens, MESH: Adult Stem Cells, Cellular differentiation, Gene Expression, MESH: Cell Cycle, MESH: Multiple Myeloma, Hematologic Cancers and Related Disorders, 0302 clinical medicine, Basic Cancer Research, Induced pluripotent stem cell, Multiple myeloma, 0303 health sciences, Induced stem cells, Multidisciplinary, Stem Cells, Cell Cycle, Genomics, Prognosis, 3. Good health, Adult Stem Cells, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, MESH: Immunologic Memory, Medicine, MESH: Pluripotent Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Multiple Myeloma, Research Article, Adult stem cell, Pluripotent Stem Cells, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Biology, MESH: Prognosis, Molecular Genetics, 03 medical and health sciences, MESH: Gene Expression Profiling, Genome Analysis Tools, Cancer stem cell, Genetics, Cancer Genetics, medicine, Humans, Genetic Testing, Myelomas and Lymphoproliferative Diseases, Genetic Association Studies, 030304 developmental biology, MESH: Humans, Gene Expression Profiling, Computational Biology, Cancers and Neoplasms, Human Genetics, medicine.disease, Immunology, Bone marrow, Immunologic Memory, Developmental Biology
Abstract: International audience; Gene expression-based scores used to predict risk in cancer frequently include genes coding for DNA replication, repair or recombination. Using two independent cohorts of 206 and 345 previously-untreated patients with Multiple Myeloma (MM), we identified 50 cell cycle-unrelated genes overexpressed in multiple myeloma cells (MMCs) compared to normal human proliferating plasmablasts and non-proliferating bone marrow plasma cells and which have prognostic value for overall survival. Thirty-seven of these 50 myeloma genes (74%) were enriched in genes overexpressed in one of 3 normal human stem cell populations--pluripotent (18), hematopoietic (10) or mesenchymal stem cells (9)--and only three genes were enriched in one of 5 populations of differentiated cells (memory B lymphocytes, T lymphocytes, polymorphonuclear cells, monocytes, osteoclasts). These 37 genes shared by MMCs and adult or pluripotent stem cells were used to build a stem cell score ((SC)score), which proved to be strongly prognostic in the 2 independent cohorts of patients compared to other gene expression-based risk scores or usual clinical scores using multivariate Cox analysis. This finding highlights cell cycle-unrelated prognostic genes shared by myeloma cells and normal stem cells, whose products might be important for normal and malignant stem cell biology.
Published: 2012
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28. Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses

Author: Bojan Polić, Thierry Walzer, Biljana Zafirova, Eric Vivier, Alfonso Martín-Fontecha, Linda S. Klavinskis, Katrina Soderquest, Graham M. Lord, King's College London School of Medicine at Guy's Hospital, Division of Immunology, Infection, and Inflammatory Diseases, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Rijeka School of Medicine, Department of Histology and Embryology, Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Melanoma, Experimental, CD8-Positive T-Lymphocytes, Lymphocyte Activation, MESH: Mice, Knockout, Mice, Interleukin 21, 0302 clinical medicine, MESH: Up-Regulation, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, Cells, Cultured, Mice, Knockout, 0303 health sciences, MESH: Pore Forming Cytotoxic Proteins, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, Up-Regulation, 3. Good health, Cell biology, Killer Cells, Natural, MESH: Melanoma, Experimental, medicine.anatomical_structure, NK Cell Lectin-Like Receptor Subfamily K, MESH: Immunologic Memory, MESH: NK Cell Lectin-Like Receptor Subfamily K, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Cells, Cultured, Pore Forming Cytotoxic Proteins, MESH: Killer Cells, Natural, MESH: Mice, Transgenic, T cell, Immunology, Mice, Transgenic, Biology, Lymphocyte Depletion, MESH: Coculture Techniques, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, Antigen-presenting cell, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, MESH: Lymphocyte Depletion, Lymphokine-activated killer cell, MESH: Humans, Perforin, NKG2D, Coculture Techniques, Mice, Inbred C57BL, Immunologic Memory, MESH: Female, 030215 immunology
Abstract: It is uncertain whether NK cells modulate T cell memory differentiation. By using a genetic model that allows the selective depletion of NK cells, we show in this study that NK cells shape CD8+ T cell fate by killing recently activated CD8+ T cells in an NKG2D- and perforin-dependent manner. In the absence of NK cells, the differentiation of CD8+ T cells is strongly biased toward a central memory T cell phenotype. Although, on a per-cell basis, memory CD8+ T cells generated in the presence or the absence of NK cells have similar functional features and recall capabilities, NK cell deletion resulted in a significantly higher number of memory Ag-specific CD8+ T cells, leading to more effective control of tumors carrying model Ags. The enhanced memory responses induced by the transient deletion of NK cells may provide a rational basis for the design of new vaccination strategies.
Published: 2011
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29. Trained immunity: a memory for innate host defense

Author: Mihai G. Netea, Jessica Quintin, Jos W. M. van der Meer, and Radboud University Medical Center [Nijmegen]
Subjects: Intrinsic immunity, Cancer Research, [SDV]Life Sciences [q-bio], animal diseases, MESH: Plants, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Adaptive Immunity, Microbiology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Immune system, MESH: Invertebrates, Immunity, Virology, Immunology and Microbiology(all), medicine, Animals, MESH: Animals, Molecular Biology, MESH: Vertebrates, Innate immune system, Host (biology), [SDV.BA]Life Sciences [q-bio]/Animal biology, Innate lymphoid cell, Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1], Plants, biochemical phenomena, metabolism, and nutrition, medicine.disease, Acquired immune system, Invertebrates, Immunity, Innate, Transplant rejection, Immunology, Vertebrates, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, bacteria, Parasitology, MESH: Immunity, Innate, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Immunologic Memory, MESH: Adaptive Immunity
Abstract: Contains fulltext : 96477.pdf (Publisher’s version ) (Closed access) Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although lacking adaptive immune responses, plants and invertebrates are protected against reinfection with pathogens, and invertebrates even display transplant rejection. In mammals, past "forgotten" studies demonstrate cross-protection between infections independently of T and B cells, and more recently memory properties for NK cells and macrophages, prototypical cells of innate immunity, have been described. We now posit that mammalian innate immunity also exhibits an immunological memory of past insults, for which we propose the term "trained immunity." Understanding trained immunity will revolutionize our view of host defense and immunological memory, and could lead to defining a new class of vaccines and immunotherapies.
Published: 2011
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30. Aberrant expression of CD6 on B-cell subsets from patients with Sjögren's syndrome

Author: Rémi Marianowski, Valérie Devauchelle, Christelle Le Dantec, Séverine Loisel, Jacques-Olivier Pers, Caroline Buors, Yves Renaudineau, Pierre Youinou, Alain Saraux, Sophie Hillion, Ruby Alonso, Enrique Montero, Experimental Immunotherapy, La Habana, Cuba, Center for molecular Immunology, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of ORL, and Laboratoire d'Immunologie et Immunothérapie
Subjects: Antigens, Differentiation, T-Lymphocyte, Cellular differentiation, Palatine Tonsil, MESH: Antigens, CD5, Cell Count, MESH: Antibodies, Monoclonal, 0302 clinical medicine, Bone Marrow, Cell Movement, Immunology and Allergy, Medicine, MESH: Antigens, CD, MESH: Cell Movement, 0303 health sciences, B-Lymphocytes, biology, Antibodies, Monoclonal, Cell Differentiation, 3. Good health, medicine.anatomical_structure, Sjogren's Syndrome, MESH: Epithelial Cells, MESH: Immunologic Memory, MESH: Palatine Tonsil, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Bone Marrow, Antibody, MESH: B-Lymphocyte Subsets, MESH: Cell Differentiation, medicine.drug_class, Immunology, B-Lymphocyte Subsets, Monoclonal antibody, CD5 Antigens, 03 medical and health sciences, Antigen, Antigens, CD, MESH: B-Lymphocytes, Humans, Cell Lineage, B cell, 030304 developmental biology, MESH: Humans, business.industry, MESH: Cell Count, Epithelial Cells, MESH: Cell Lineage, B-1 cell, MESH: Sjogren's Syndrome, MESH: Antigens, Differentiation, T-Lymphocyte, biology.protein, Bone marrow, CD5, business, Immunologic Memory, 030215 immunology
Abstract: International audience; CD6 is one of a pair of related genes encoding CD5-associated receptors on all T cells and a subset of B cells. The current availability of "T1h", a humanized anti-CD6 monoclonal antibody for B cell-mediated autoimmune disorders revives analysis of the B-cell subset expression of CD6, particularly in primary Sjögren's syndrome (SS). Refined phenotype of B-lymphocytes peripheral blood (PB), bone marrow and tonsils revealed that the overlap between the expression of CD6 is less close to that of CD5 than currently acknowledged. In contrast to CD5, CD6 is absent on transitional B cells, while present on mature and memory B cells. Interestingly, the PB proportion of CD6(+) B cells is decreased in patients with primary SS, as opposed to those with rheumatoid arthritis. The reduction in primary SS does not result from the shedding of CD6 from the membrane of B cells, but from the lowering of memory B lymphocytes. It may result from the ability of CD6 to make transmigration of CD27(+) memory B cells into the salivary glands (SGs) easier. Consistent with this view is our finding that CD166 (one of the ligands for CD6) is highly expressed on epithelial cells of patients' SGs. This study is relevant in that the humanized T1h anti-CD6 becomes an alternative to anti-CD20 for treatment of primary SS.
Published: 2010
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31. Memory B-cell aggregates in skin biopsy are diagnostic for primary Sjögren's syndrome

Author: Laurent Misery, Gabriel J. Tobón, Pierre Youinou, Gilles Lemasson, Valérie Devauchelle, Anne-Marie Roguedas, Alain Saraux, Jacques-Olivier Pers, Service de dermatologie, Hôpital Augustin Morvan-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Neurosciences de Brest (LNB), Université de Brest (UBO), Laboratoire d'Immunologie et Immunothérapie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Michel, Geneviève
Subjects: Systemic disease, Pathology, Biopsy, Salivary Glands, MESH: Biopsy, Cell Movement, Immunopathology, Immunology and Allergy, Medicine, Memory B cell, MESH: Antigens, CD, MESH: Cell Movement, Skin, CD20, MESH: Aged, B-Lymphocytes, MESH: Middle Aged, medicine.diagnostic_test, biology, integumentary system, Anatomical pathology, Cell Differentiation, Middle Aged, Sjogren's Syndrome, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Salivary Glands, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Sweat Glands, Immunology, MESH: Skin, Antigens, CD, MESH: B-Lymphocytes, Humans, Aged, MESH: Humans, business.industry, MESH: Adult, medicine.disease, Sweat Glands, MESH: Sjogren's Syndrome, Skin biopsy, biology.protein, Histopathology, business, Immunologic Memory, MESH: Female
Abstract: International audience; There is a crucial need for reliable diagnostic criteria for SS. Our objective was to evaluate the frequency of xerosis in patients with primary Sjögren's syndrome (SS), and compare histopathology of cutaneous sweat glands and labial salivary glands (LSGs), with respect to their contribution to the diagnosis. Twenty-two patients with primary SS and 22 matched normal volunteers were invited to rate their skin dryness on a visual analog scale. The skin was dryer (58.3 ± 10.1 versus 38.9 ± 7.6, P < 0.01), and xerosis more frequent (9 of 22 versus 2 of 22, P < 0.02) in the patients than in the controls. The axilla skin was chosen for a 6-mm punch biopsy. Lymphocytic infiltration was seen in the skin of 8 of the 12 patients tested. Two of them had normal LSGs. Most interestingly, B cell infiltrates were identified in patients' skin infiltrates, so that their presence might be a clue to the diagnosis of primary SS. These cell aggregates associated memory CD10-/CD20+/CD27+/IgD- B lymphocytes and immature CD20+/CD24 + lymphocytes. These latter findings strongly suggest that skin biopsies warrant inclusion into the routine clinical care of patients suspected of suffering from primary SS.
Published: 2010

32. Th17 Cells Are the Dominant T Cell Subtype Primed by Shigella flexneri Mediating Protective Immunity

Author: Gérard Eberl, Jörg H. Fritz, Antonio Bandeira, Armelle Phalipon, Wilmara Salgado-Pabón, Phillippe J. Sansonetti, James P. Di Santo, Joao G. Magalhaes, Gernot Sellge, Christoph Konradt, Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Department of Immunology, University of Toronto, Développement des Tissus Lymphoïdes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Développement des Lymphocytes, Cytokines et Développement Lymphoïde, Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), The work was supported by a grant of the German Research Foundation (SE1122/1-1), a Marie Curie Intra-European Fellowships grant (no. 011192), a Bourse Roux from the Institute Pasteur, and an Institut Pasteur grant (PTR 154)., We thank Myriam Tanguy for technical assistance, Allison Marty for critical reading of this manuscript, Anne Thiebaut and Claire Bernède-Baudin for help in the statistical analysis, Matthias Lochner for genotyping of Rorc(γt)-GfpTG mice and helpful discussion, and Mathew Alberts and Helene Saklani for providing IL-12/23p40° mice., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Chaire Microbiologie et Maladies infectieuses
Subjects: MESH: Shigella flexneri, MESH: Interleukin-17, Priming (immunology), MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, Shigella flexneri, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, MESH: Animals, Cells, Cultured, Mice, Knockout, 0303 health sciences, biology, Interleukin-17, T-Lymphocytes, Helper-Inducer, Acquired immune system, 3. Good health, medicine.anatomical_structure, Interleukin 12, MESH: Immunologic Memory, MESH: Cells, Cultured, MESH: Dysentery, Bacillary, MESH: Mice, Transgenic, T cell, Secondary infection, Immunology, MESH: Immunodominant Epitopes, Mice, Transgenic, chemical and pharmacologic phenomena, Microbiology, 03 medical and health sciences, Th2 Cells, MESH: Mice, Inbred C57BL, MESH: Th2 Cells, medicine, Animals, MESH: T-Lymphocytes, Helper-Inducer, MESH: Mice, Dysentery, Bacillary, 030304 developmental biology, MHC class II, Immunodominant Epitopes, Th1 Cells, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mice, Inbred C57BL, MESH: Th1 Cells, biology.protein, Immunologic Memory, CD8, 030215 immunology
Abstract: The T cell response to Shigella, the causative agent of bacillary dysentery, remains poorly understood. Using a murine model of infection, we report that Shigella flexneri primes predominately IL-17A– and IL-22–producing Th17 cells. Shigella-specific Th1 cells are only significantly induced on secondary infection, whereas specific Th2 and CD8+ T cells are undetectable. Apart from Th17 cells that are primed in a MHC class II- and IL-6–dependent, but IL12/23p40-independent manner, we identified γδ T cells as an additional but minor source of IL-17A. Priming of IL-17A+ γδ T cells is dependent on IL12/23p40, but independent of MHC-class II and IL-6. Th17 cells have emerged as important players in inflammatory, autoimmune, and infectious diseases. Among the yet unresolved questions is their role in long-term immunity to pathogens. In this study, we show that the elicited S. flexneri-specific Th17 pool gives rise to an enhanced recall response up to 12 mo after priming, suggesting the presence of a long-term memory state. The clearance of primary infection is impaired in the absence of T cells, but independently of IL-17A. However, after reinfection, IL-17A produced by S. flexneri-specific Th17 cells becomes important to ultimately restrict bacterial growth. These findings bring new insights into the adaptive immune response to Shigella infection and highlight the importance of pathogen-specific Th17 cell immunity for secondary immune protection.
Published: 2010
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33. An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization

Author: Marion Larroque, John De Vos, Michel Jourdan, Anouk Caraux, Geneviève Fiol, Dirk Hose, Christophe Duperray, Caroline Bret, Chantal Cognot, Bernard Klein, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Laboratoire d'immunologie, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Nationales Centrum für Tumorerkrankungen, Grant from the Ligue Nationale Contre le Cancer (equipe labellisee 2009), INCA, MSCNET European strep (n°e06005ff), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Frei, Monique
Subjects: X-Box Binding Protein 1, Time Factors, MESH: Immunoglobulins, plasma cell, Cellular differentiation, Cell Culture Techniques, MESH: Flow Cytometry, Plasma cell, Biochemistry, Immunophenotyping, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, Activation-induced (cytidine) deaminase, Cells, Cultured, Oligonucleotide Array Sequence Analysis, B-Lymphocytes, 0303 health sciences, MESH: Plasma Cells, biology, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, MESH: Bone Marrow Cells, Cell Differentiation, Hematology, MESH: Transcription Factors, Flow Cytometry, humanities, 3. Good health, DNA-Binding Proteins, multiple myeloma, medicine.anatomical_structure, Interferon Regulatory Factors, Proto-Oncogene Proteins c-bcl-6, MESH: Immunologic Memory, Antibody, Stem cell, MESH: Interferon Regulatory Factors, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Immunophenotyping, MESH: Syndecan-1, Plasma Cells, Immunology, MESH: B-Cell-Specific Activator Protein, Immunoglobulins, Bone Marrow Cells, Regulatory Factor X Transcription Factors, MESH: Stem Cells, Models, Biological, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, Cytidine Deaminase, transcription factors, MESH: B-Lymphocytes, PRDM1, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Cytidine Deaminase, MESH: Cell Culture Techniques, MESH: Humans, B lymphocyte, Gene Expression Profiling, MESH: Time Factors, PAX5 Transcription Factor, MESH: Models, Biological, Cell Biology, Molecular biology, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, Syndecan-1, Bone marrow, Immunologic Memory, MESH: DNA-Binding Proteins, 030215 immunology
Abstract: Abstract 1636 Poster Board I-662 Human plasma cells (PCs) and their precursors play an essential role in humoral immune response, but are rare and difficult to harvest. We report here i) the generation of human syndecan-1+ and immunoglobulin secreting PCs starting from memory B cells (MBCs) in a 3-step- and 10-day (D) culture, including a 6-fold cell amplification. ii) We report the detailed phenotypic and Affymetrix gene expression profiles of these in vitro PCs as well as of intermediate cells - activated B cells (actBCs) and plasmablasts (PBs) - compared to MBCs and bone marrow PCs, which is accessible through an open web ATLAS (http://amazonia.transcriptome.eu/). iii) We show this B cell to PC differentiation to involve IRF4 and AICDA expression in D4 actBCs, decrease of PAX5 and BCL6 expressions and increase in PRDM1 and XBP1 expressions in D7 PBs and D10 PCs. It involves downregulation of genes controlled by Pax5, induction of genes controlled by Blimp-1 and XBP1 (unfold protein response). iv) The phenotype of D10 PCs resembles that of peripheral blood PCs detected after immunization of healthy donors. This in vitro model will facilitate further studies in PC biology. It will likewise be helpful to study plasma-cell dyscrasias, including Multiple Myeloma. Disclosures No relevant conflicts of interest to declare.
Published: 2009
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34. Epitope specificity and relative clonal abundance do not affect CD8 differentiation patterns during lymphocytic choriomeningitis virus infection

Author: James P. Di Santo, Hélène Decaluwe, Benedita Rocha, Ivana Munitic, Agnes Le Bon, César Evaristo, Sara Lemos, Myriam F. Wlodarczyk, Liisa K. Selin, Yves Rivière, Andrew Worth, Persephone Borrow, Differenciation Thymique et Physiologie des Lymphocytes T (U591), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Immunopathologie Virale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Nuffield Department of Clinical Medicine, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Lymphocytic Choriomeningitis, Immunology, Receptors, Antigen, T-Cell, Epitopes, T-Lymphocyte, Immunodominance, CD8-Positive T-Lymphocytes, Lymphocytic Choriomeningitis, Biology, Lymphocytic choriomeningitis, Microbiology, Epitope, MESH: Epitopes, T-Lymphocyte, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Virology, Virus latency, medicine, CD8 T cells, clonal abundance, T cell differentiation, lymphocytic choriomeningitis virus infection, Animals, Lymphocytic choriomeningitis virus, MESH: Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Mice, 030304 developmental biology, 0303 health sciences, T-cell receptor, MESH: Virus Latency, MESH: Receptors, Antigen, T-Cell, medicine.disease, MESH: CD8-Positive T-Lymphocytes, MESH: Gene Expression Regulation, Virus Latency, Gene Expression Regulation, Insect Science, MESH: Immunologic Memory, Pathogenesis and Immunity, MESH: Lymphocytic choriomeningitis virus, Immunologic Memory, CD8, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030215 immunology
Abstract: To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all CD8 effector genes simultaneously in single cells. Surprisingly, these methods failed to reveal a major impact of clonal dominance in CD8 properties throughout the response. Aiming to increase clonal dominance, we examined high-frequency transferred P14 T-cell receptor transgenic (TCR Tg) cells. Under these conditions LCMV is cleared faster, and accordingly we found an accelerated response. However, when Tg and endogenous cells were studied in the same mice, where they should be subjected to the same antigen load, they showed overlapping properties, and the presence of P14 cells did not modify endogenous responses to other LCMV epitopes or a perturbed immunodominance hierarchy in the memory phase. Using allotype-labeled Tg cells, we found that during acute infection up to 80% downregulated their TCR and were undetectable by tetramer binding, and that tetramer-negative and tetramer-positive cells had very different features. Since Tg cells are not available to evaluate immune responses in humans and, in many cases, are not available from the mouse, the tetramer-based evaluation of early immune responses in most situations of high viremia may be incomplete and biased.
Published: 2009
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35. Expression of genes encoding for proteins involved in heparan sulphate and chondroitin sulphate chain synthesis and modification in normal and malignant plasma cells

Author: Jean-François Rossi, Caroline Bret, Hartmut Goldschmidt, Bernard Klein, Dirk Hose, Jean-François Schved, Anne-Catherine Sprynski, Karène Mahtouk, Thierry Rème, Philippe Quittet, Laboratoire d'immunologie, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], National Center for Tumor Diseases (NCTD), CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), and Frei, Monique
Subjects: glycosaminoglycan synthesis and modification pathways, chondroitin sulphate, MESH: Chondroitin Sulfates, Gene Expression, MESH: Multiple Myeloma, Kaplan-Meier Estimate, Syndecan 1, Glycosaminoglycan, heparan sulphate, Gene expression, MESH: Kaplan-Meiers Estimate, Oligonucleotide Array Sequence Analysis, 0303 health sciences, B-Lymphocytes, Principal Component Analysis, MESH: Plasma Cells, Hematology, biology, 030302 biochemistry & molecular biology, Chondroitin Sulfates, food and beverages, Prognosis, MESH: Case-Control Studies, multiple myeloma, Biochemistry, MESH: Immunologic Memory, proteoglycans, medicine.medical_specialty, MESH: Cell Line, Tumor, MESH: Gene Expression, MESH: Syndecan-1, Plasma Cells, Article, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Heparitin Sulfate, Internal medicine, Cell Line, Tumor, MESH: B-Lymphocytes, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, 030304 developmental biology, MESH: Principal Component Analysis, MESH: Humans, Heparan sulphate, Gene Expression Profiling, Gene expression profiling, carbohydrates (lipids), Proteoglycan, Case-Control Studies, MESH: Protein Processing, Post-Translational, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, Heparitin Sulfate, Syndecan-1, Immunologic Memory, Protein Processing, Post-Translational
Abstract: International audience; Syndecan-1 is a proteoglycan that concentrates heparin-binding factors on the surface of multiple myeloma cells, and probably plays a major role in multiple myeloma biology. As heparan sulphate and chondroitin sulphate are the bioactive components of syndecan-1, we analysed the signature of genes encoding 100 proteins involved in synthesis of these chains, i.e. from precursor uptake to post-translational modifications, using Affymetrix microarrays. The expression of enzymes required for heparan sulphate and chondroitin sulphate biosynthesis was shown to increase in parallel with syndecan-1 expression, throughout the differentiation of memory B cells into plasmablasts and normal bone marrow plasma cells. Sixteen genes were significantly different between normal and malignant plasma cells, nine of these genes -EXT2, CHSY3, CSGALNACT1, HS3ST2, HS2ST1, CHST11, CSGALNACT2, HPSE, SULF2 - encode proteins involved in glycosaminoglycan chain synthesis or modifications. Kaplan-Meier analysis was performed in two independent series of patients: B4GALT7, CSGALNACT1, HS2ST1 were associated with a good prognosis whereas EXT1 was linked to a bad prognosis. This study provides an overall picture of the major genes encoding for proteins involved in heparan sulphate and chondroitin sulphate synthesis and modifications that can be implicated in normal and malignant plasma cells.
Published: 2009
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36. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment

Author: Jean-François Delfraissy, Cécile Goujard, François Boué, Thérèse Croughs, Rodolphe Thiébaut, Christine Lacabaratz, Jean-Michel Molina, Yves Levy, Jean-Daniel Lelièvre, Stéphanie Beq, Véronique Avettand-Fenoel, Jean-Paul Viard, Geneviève Chêne, Christine Rouzioux, Laurence Weiss, Michel Morre, Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri-Mondor Albert-Chenevier, Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cythéris, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Henri-Mondor Albert-Chenevier, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Santé Publique, d'Epidémiologie et de Développement ( ISPED ), and Guellaen, Georges
Subjects: MESH: CD4 Lymphocyte Count, medicine.medical_treatment, T-Lymphocytes, Cell, MESH : Aged, MESH : Prospective Studies, CD4-CD8 Ratio, HIV Infections, MESH: Cell Cycle, Lymphocyte Activation, MESH: Recombinant Proteins, MESH: HIV-1, 0302 clinical medicine, Prospective Studies, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Cell Cycle, General Medicine, Drug Tolerance, MESH: HIV Infections, MESH : Adult, Cell cycle, Middle Aged, Recombinant Proteins, 3. Good health, medicine.anatomical_structure, MESH: Immunologic Memory, MESH : Lymphopenia, Safety, MESH : HIV-1, Research Article, MESH : Interleukin-7, Adult, MESH : Recombinant Proteins, MESH : Immunologic Memory, T cell, MESH: Drug Tolerance, MESH: Lymphopenia, 03 medical and health sciences, Antigen, Lymphopenia, MESH : Cell Cycle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : CD4 Lymphocyte Count, MESH : HIV Infections, medicine, Humans, MESH : Middle Aged, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Safety, MESH: Lymphocyte Activation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Lymphocyte Activation, 030304 developmental biology, Aged, MESH : T-Lymphocytes, MESH: Humans, business.industry, Interleukin-7, MESH : Humans, MESH: Safety, MESH: Adult, Immunotherapy, medicine.disease, T cell deficiency, MESH: Interleukin-7, MESH: Prospective Studies, CD4 Lymphocyte Count, MESH: T-Lymphocytes, MESH : CD4-CD8 Ratio, MESH : Drug Tolerance, Immunology, HIV-1, MESH: CD4-CD8 Ratio, business, Immunologic Memory, CD8, 030215 immunology
Abstract: International audience; HIV infection results in CD4+ T cell deficiency, but efficient combination antiretroviral therapy (c-ART) restores T cells and decreases morbidity and mortality. However, immune restoration by c-ART remains variable, and prolonged T cell deficiency remains in a substantial proportion of patients. In a prospective open-label phase I/IIa trial, we evaluated the safety and efficacy of administration of the T cell regulator IL-7. The trial included 13 c-ART-treated HIV-infected patients whose CD4+ cell counts were between 100 and 400 cells/microl and plasma HIV RNA levels were less than 50 copies/ml. Patients received a total of 8 subcutaneous injections of 2 different doses of recombinant human IL-7 (rhIL-7; 3 or 10 microg/kg) 3 times per week over a 16-day period. rhIL-7 was well tolerated and induced a sustained increase of naive and central memory CD4+ and CD8+ T cells. In the highest dose group, 4 patients experienced transient increases in viral replication. However, functional assays showed that the expanded T cells responded to HIV antigen by producing IFN-gamma and/or IL-2. In conclusion, in lymphopenic HIV-infected patients, rhIL-7 therapy induced substantial functional and quantitative changes in T cells for 48 weeks. Therefore, patients may benefit from intermittent therapy with IL-7 in combination with c-ART.
Published: 2009
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37. Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions

Author: Bertrand Dubois, Florentin-Martial Mbitikon-Kobo, Antoine Marçais, Sophia Djebali, Charles-Antoine Coupet, Christophe Arpin, Marc Vocanson, Jean-François Nicolas, Marie-Cécile Michallet, Martine Tomkowiak, Nathalie Bonnefoy-Berard, Georgi S. Angelov, Jacqueline Marvel, Anne Cottalorda, Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and Fargeot, Alexandra
Subjects: Priming (immunology), MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Dermatitis, Contact, Lymphocyte Activation, MESH: Mice, Knockout, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, Mice, Knockout, 0303 health sciences, biology, Cell Differentiation, MESH: CD8-Positive T-Lymphocytes, MESH: Interleukin-2 Receptor beta Subunit, Hyaluronan Receptors, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Inflammation Mediators, MESH: Cell Differentiation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, MESH: Inflammation Mediators, Immunology, Eomesodermin, Mice, Transgenic, MESH: Antigens, CD44, CCL5, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Dermatitis, Contact, medicine, Animals, Secretion, MESH: Lymphocyte Activation, MESH: Mice, Allergic contact dermatitis, 030304 developmental biology, Recall, CD44, MESH: Biological Markers, medicine.disease, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, biology.protein, Immunologic Memory, Biomarkers, 030215 immunology
Abstract: Most memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122int memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-γ secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122high memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.
Published: 2009
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38. Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets

Author: Matthieu Carrière, Armand Bensussan, Maria Nikolova, Yves Levy, Jean-Daniel Lelièvre, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, National Center of Infectious and Parasitic Diseases, National Center of Infectious and Parasitic Diseases [Sofia, Bulgarie] (NCIPD), Immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri-Mondor Albert-Chenevier, and Guellaen, Georges
Subjects: MESH: Signal Transduction, Cellular differentiation, Programmed Cell Death 1 Receptor, MESH: Flow Cytometry, Apoptosis, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, MESH: Monocytes, Biochemistry, T-Lymphocytes, Regulatory, B7-H1 Antigen, Monocytes, Interleukin 21, 0302 clinical medicine, T-Lymphocyte Subsets, Cytotoxic T cell, IL-2 receptor, MESH: Antigens, CD, MESH: Cytokines, 0303 health sciences, biology, Effector, hemic and immune systems, Cell Differentiation, Hematology, Flow Cytometry, MESH: CD8-Positive T-Lymphocytes, Cell biology, MESH: Immunologic Memory, Cytokines, Signal Transduction, MESH: Cell Differentiation, MESH: Immunophenotyping, Immunology, chemical and pharmacologic phenomena, Article, Immunophenotyping, 03 medical and health sciences, Immune system, Antigens, CD, MESH: Cell Proliferation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Cell Proliferation, MESH: Humans, CD40, MESH: Apoptosis Regulatory Proteins, MESH: Apoptosis, MESH: T-Lymphocytes, Regulatory, Cell Biology, biology.protein, Apoptosis Regulatory Proteins, Immunologic Memory, CD8, 030215 immunology
Abstract: The balanced manifestation of effector functions and the generation of long-living memory cells is a hallmark of efficient CD8+ T-cell response. Accumulating data pinpoint CD4+ CD25high regulatory T (Treg) cells as a key factor for the inefficiency of CD8+ T-cell responses in viral persistence. Little is known about the effects of Treg cells on the homeostasis of healthy donor CD8+ T cells. The present study demonstrates that Treg cells exert differential effects on CD8+ T-cell subsets. Treg cells inhibited mostly the polyclonal proliferation of CD27− effector cells compared with CD27+ memory CD8+ T cells. Moreover, they inhibited the polyclonal and antigen-driven differentiation of memory cells into functional effectors as defined by IFN-γ secretion and induction of CD160 expression. Finally, Treg cells reduced the apoptosis of memory but not of effector and terminal effector cell populations. These effects were at least in part mediated by a decreased expression of PD-L1, but not of programmed death 1 (PD-1), on CD8+ T cells after activation. Thus, in the setting of a healthy immune system, Treg cells fine-tune the memory/effector cell balance and promote the accumulation of long-living memory cells in case of strong stimulation.
Published: 2009
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39. Immunology: Natural killer cells remember

Author: Ugolini, Sophie, Vivier, Eric, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital de la Timone [CHU - APHM] (TIMONE), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Killer Cells, Natural, MESH: Adoptive Transfer, MESH: T-Lymphocytes, MESH: B-Lymphocytes, MESH: Cell Proliferation, MESH: Immunologic Memory, MESH: Muromegalovirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Immunity, Innate, MESH: Mice, MESH: Models, Immunological, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2009
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40. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses

Author: Carl De Trez, Magdalena Radwanska, Samuel J. Black, Bernard Ryffel, Stefan Magez, Patrick Guirnalda, Laboratoire de Parasitologie, Université libre de Bruxelles (ULB), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Department of Molecular and Cellular Interactions, Cellular and Molecular Immunology, and Department of Bio-engineering Sciences
Subjects: Vaccines -- administration & dosage, Bordetella pertussis, MESH: Spleen, Immunology/Immunomodulation, Antibodies, Protozoan, Gene Expression, Apoptosis, MESH: Flow Cytometry, Dendritic Cells -- immunology, MESH: Animals, Newborn, Mice, 0302 clinical medicine, Immunology/Cellular Microbiology and Pathogenesis, MESH: Animals, Biology (General), 0303 health sciences, education.field_of_study, B-Lymphocytes, Vaccines, Mice, Inbred BALB C, MESH: Dendritic Cells, Trypanosomiasis, African -- immunology, Cell Biology/Cellular Death and Stress Responses, Sciences bio-médicales et agricoles, Flow Cytometry, 3. Good health, Antibodies, Protozoan -- biosynthesis, medicine.anatomical_structure, Infectious Diseases, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Research Article, Trypanosoma brucei brucei -- immunology, MESH: Gene Expression, MESH: Immunophenotyping, QH301-705.5, Dendritic Cells -- parasitology, Immunology, Population, Trypanosoma brucei brucei, MESH: Mice, Inbred BALB C, Spleen, Spleen -- pathology, Biology, Trypanosoma brucei, Microbiology, MESH: Host-Parasite Interactions, Host-Parasite Interactions, Immunophenotyping, 03 medical and health sciences, Immune system, Virology, Immunology/Immunity to Infections, MESH: B-Lymphocytes, MESH: Cell Proliferation, Genetics, medicine, Antigenic variation, Trypanosoma brucei brucei -- pathogenicity, Animals, MESH: Antibodies, Protozoan, RNA, Messenger, education, Molecular Biology, B-Lymphocytes -- pathology, MESH: Mice, B cell, 030304 developmental biology, Cell Proliferation, MESH: RNA, Messenger, MESH: Apoptosis, Infectious Diseases/Protozoal Infections, Germinal center, MESH: Trypanosoma brucei brucei, Dendritic Cells, RC581-607, biology.organism_classification, RNA, Messenger -- metabolism, MESH: Vaccines, Disease Models, Animal, Trypanosomiasis, African, MESH: Trypanosomiasis, African, Infectious Diseases/Neglected Tropical Diseases, Animals, Newborn, Immunologic Memory -- immunology, Parasitology, Immunologic diseases. Allergy, MESH: Disease Models, Animal, Immunologic Memory, 030215 immunology, Spleen -- immunology
Abstract: African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM(+) marginal zone (IgM(+)MZ) B cell population characterized as B220(+)IgM(High)IgD(Int) CD21(High)CD23(Low)CD1d(+)CD138(-). These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM(+) B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T-cell independent IgM(+)MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2008
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41. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells

Author: Mamani-Matsuda, Maria, Cosma, Antonio, Weller, Sandra, Faili, Ahmad, Staib, Caroline, Garçon, Loïc, Hermine, Olivier, Beyne-Rauzy, Odile, Fieschi, Claire, Pers, Jacques-Olivier, Arakelyan, Nina, Varet, Bruno, Sauvanet, Alain, Berger, Anne, Paye, François, Andrieu, Jean-Marie, Michel, Marc, Godeau, Bertrand, Buffet, Pierre, Reynaud, Claude-Agnès, Weill, Jean-Claude, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinical cooperation group 'Immune monitoring', German Research Center for Environmental Health - Helmholtz Center München (GmbH), Clinical cooperation group 'Antigen-specific immunotherapy', Institute of Molecular Virology, Institute of Virology, Technical University, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne et Immunopathologie, CHU Toulouse [Toulouse], Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'oncologie médicale [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], This work was supported by the Fondation Princesse Grace, the Agence Nationale pour la Recherche ('B cell memory', MIIM program) and the Ligue Contre le Cancer (Equipe labellisée). M.M.-M. was supported by successive fellowships from the Fondation de France, the Fondation Singer-Polignac and the Région Ile-de- France, ANR-07-BLAN-0099,BcellMemory,FUNCTIONAL CHARACTERIZATION OF MEMORY B CELLS(2007), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Médical de l'Institut Pasteur (CMIP), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)
Subjects: MESH: Immunoglobulin G, MESH: Humans, MESH: Spleen, MESH: B-Lymphocytes, MESH: Vaccinia virus, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Splenectomy, MESH: Case-Control Studies
Abstract: International audience; The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG(+) cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG(+) cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG(+) B cells in blood (ie, 50-100,000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell-depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory--long-lived memory B cells and plasma cells--have specific anatomic distributions--spleen and bone marrow--and homeostatic regulation.
Published: 2008
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42. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells

Author: Arlette Tridon, Martine Pernollet, Josette Péguet-Navarro, Christian Drouet, Nicole Monnier, Marie-Bernadette Villiers, Denis Gerlier, Arije Ghannam, Joël Lunardi, Denise Ponard, Jean-Luc Fauquert, Roux-Buisson, Nathalie, Virologie et Pathologie Humaine (VirPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang, EFS, CHU Clermont-Ferrand, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'immunohistochimie, CHU Grenoble-Hôpital Michallon, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Fonctions Normales et Pathologiques de la Barrière Cutanée [Hôpital Edouard Herriot - HCL], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Groupe de Recherche et d’Étude du Processus Inflammatoire (TIMC-IMAG-GREPI), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), the French Ministry of Health, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), GREPI, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Virologie et Pathologie Humaine ( VirPath ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Duperray, Alain, and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Male, MESH : Coculture Techniques, Dendritic cell differentiation, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, T-Lymphocytes, Regulatory, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, MESH : Child, MESH: Child, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Child, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Cells, Cultured, 0303 health sciences, Immunity, Cellular, biology, MESH: Dendritic Cells, ZAP70, MESH: Complement C3, Cell Differentiation, MESH : Infant, Complement C3, MESH : Adult, MESH : Immunity, Innate, Natural killer T cell, MESH: Infant, Pedigree, medicine.anatomical_structure, Child, Preschool, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH : Complement C3, MESH: B-Lymphocyte Subsets, MESH : Cell Differentiation, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, medicine.medical_specialty, Regulatory T cell, MESH : Immunologic Memory, MESH: Pedigree, MESH : Male, Immunology, B-Lymphocyte Subsets, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Immunity, Cellular, MESH: Coculture Techniques, 03 medical and health sciences, Internal medicine, MESH : Cells, Cultured, medicine, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, CD40, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH: Child, Preschool, Infant, MESH : Immunity, Cellular, MESH: Adult, Dendritic Cells, Coculture Techniques, Immunity, Innate, MESH: Male, B-1 cell, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH : Pedigree, MESH : Dendritic Cells, biology.protein, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Immunologic Memory, 030215 immunology, MESH : B-Lymphocyte Subsets
Abstract: Primary C3 deficiency, a rare autosomal inherited disease (OMIM 120700), was identified in a 2-year-old male suffering from recurrent pyogenic infections from early infancy with undetectable total complement hemolytic activity (CH50) and C3 values. The nonconsanguineous parents and the two patients’ two siblings had 50% normal serum C3 concentration. The molecular abnormality associated a paternal allele coding C3 with the missense mutation p.Ser550Pro and an apparently null maternal allele, with production of a defective protein that could no longer be secreted. Vaccination of the child did not induce a long-term Ab response. Accordingly, switched memory IgD−CD27+ B cells were barely detected, amounting to only 2.3% of peripheral blood CD19+ cells. Cells were significantly defective in stimulating alloreactive responses. The in vitro development of immature dendritic cells and their maturation capacity were greatly impaired, with decreased CD1a expression and IL-12p70 secretion ability. These cells were unable to induce autologous B cell proliferation and Ig secretion in the presence of CD40L and C3. Finally, the regulatory T cell development ability of CD4+ T cells after CD3 and CD46 activation in the presence of IL-2 was significantly impaired. Thus, the association of important functional defects of dendritic cells, acquisition of B cell memory, and regulatory T cells with human C3 deficiency strongly supports a major role for C3 in bridging innate and adaptive immunity in humans.
Published: 2008

43. Pathophysiological aspects of memory B-cell development

Author: Olivier Hermine, Sandrine Roulland, Bertrand Nadel, Felipe Suarez, Slama, Catherine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Immunoglobulins, Cellular differentiation, T-Lymphocytes, Follicular lymphoma, Hepacivirus, MESH : Hepacivirus, MESH : Immunoglobulins, MESH: Lymphoma, Follicular, 0302 clinical medicine, MESH: Germinal Center, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Hepacivirus, Memory B cell, MESH: Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Plasma Cells, B-Lymphocytes, Cell Differentiation, Marginal zone, Antigens, T-Independent, MESH : Antigens, T-Independent, MESH : Lymphoma, B-Cell, Marginal Zone, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Immunologic Memory, MESH : Helicobacter pylori, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH : Plasma Cells, MESH : Immunologic Memory, Immunology, Plasma Cells, Immunoglobulins, Biology, MESH : B-Lymphocytes, 03 medical and health sciences, Antigen, MESH: B-Lymphocytes, medicine, Animals, Humans, B cell, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, Helicobacter pylori, MESH : Lymphoma, Follicular, MESH : Humans, Germinal center, Lymphoma, B-Cell, Marginal Zone, medicine.disease, Germinal Center, Lymphoma, MESH: T-Lymphocytes, MESH: Antigens, T-Independent, MESH: Helicobacter pylori, MESH : Animals, MESH : Germinal Center, Immunologic Memory
Abstract: B cells follow two functionally distinct pathways of development: a classical germinal center (GC) T-dependent pathway in which diversification and maturation generate a slow, but virtually unlimited high-affinity response to cognate antigens; and a marginal zone (MZ) T-independent pathway providing a first line of 'innate-like' defense against specific pathogens. Cells populating these two distinct locations are the normal counterparts of two clinically important pathological entities, follicular lymphoma (FL) and MZ lymphoma (MZL). FL and MZ represent paradigms of two rising concepts of lymphomagenesis, protracted preclinical and antigen-driven lymphoproliferation, respectively. Integrating the mechanisms and functions of MZ and GC B cells and the distinctive features of their pathological counterparts should provide essential clues to the understanding of their malignant development, and should offer new insights into the design of effective treatments for B-cell lymphomas.
Published: 2008
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44. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells.: Long-lived B cell memory in the spleen

Author: Mamani-Matsuda, Maria, Cosma, Antonio, Weller, Sandra, Faili, Ahmad, Staib, Caroline, Garçon, Loïc, Hermine, Olivier, Beyne-Rauzy, Odile, Fieschi, Claire, Pers, Jacques-Olivier, Arakelyan, Nina, Varet, Bruno, Sauvanet, Alain, Berger, Anne, Paye, François, Andrieu, Jean-Marie, Michel, Marc, Godeau, Bertrand, Buffet, Pierre, Reynaud, Claude-Agnès, Weill, Jean-Claude, Mamani-Matsuda, Maria, Blanc - FUNCTIONAL CHARACTERIZATION OF MEMORY B CELLS - - BcellMemory2007 - ANR-07-BLAN-0099 - BLANC - VALID, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinical cooperation group 'Immune monitoring', German Research Center for Environmental Health - Helmholtz Center München (GmbH), Clinical cooperation group 'Antigen-specific immunotherapy', Institute of Molecular Virology, Institute of Virology, Technical University, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), This work was supported by the Fondation Princesse Grace, the Agence Nationale pour la Recherche ('B cell memory', MIIM program) and the Ligue Contre le Cancer (Equipe labellisée). M.M.-M. was supported by successive fellowships from the Fondation de France, the Fondation Singer-Polignac and the Région Ile-de- France, and ANR-07-BLAN-0099,BcellMemory,FUNCTIONAL CHARACTERIZATION OF MEMORY B CELLS(2007)
Subjects: MESH: Immunoglobulin G, MESH: Humans, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Spleen, MESH: B-Lymphocytes, MESH: Vaccinia virus, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Splenectomy, MESH: Case-Control Studies
Abstract: International audience; The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG(+) cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG(+) cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG(+) B cells in blood (ie, 50-100,000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell-depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory--long-lived memory B cells and plasma cells--have specific anatomic distributions--spleen and bone marrow--and homeostatic regulation.
Published: 2008
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45. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes

Author: Laura Campisi, Delphine Bassand, Grégoire Lauvau, Pierre Gounon, Emilie Narni-Mancinelli, Nicolas Glaichenhaus, Julie Cazareth, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), and INSERM (Avenir), Human Frontier Science Program (CDA), Agence Nationale de la Recherche (ANR-IRAP-2005), Fondation pour la Recherche Médicale (FRM)
Subjects: Cytotoxicity, Immunologic, Chemokine, Time Factors, Neutrophils, MESH: Neutrophils, CD8-Positive T-Lymphocytes, MESH: Listeria monocytogenes, MESH: Phagocytes, Mice, 0302 clinical medicine, MESH: Leishmania major, Immunology and Allergy, Cytotoxic T cell, Interferon gamma, MESH: Animals, Listeriosis, Chemokine CCL4, MESH: Bacterial Proteins, MESH: Immunity, Chemokine CCL3, Leishmania major, 0303 health sciences, Phagocytes, biology, Effector, MESH: Bystander Effect, MESH: Reactive Oxygen Species, MESH: Tumor Necrosis Factors, Articles, Macrophage Inflammatory Proteins, MESH: CD8-Positive T-Lymphocytes, MESH: Chemokines, CC, Chemokines, CC, Tumor Necrosis Factors, MESH: Immunologic Memory, MESH: Immunization, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Female, MESH: Listeria Infections, medicine.drug, MESH: Mutation, MESH: Interferon Type II, MESH: Macrophage Inflammatory Proteins, Secondary infection, Immunology, MESH: Models, Immunological, Article, Microbiology, 03 medical and health sciences, Interferon-gamma, Bacterial Proteins, medicine, Animals, MESH: Chemokine CCL3, MESH: Cytotoxicity, Immunologic, MESH: Chemokine CCL4, MESH: Mice, 030304 developmental biology, Innate immune system, Tumor Necrosis Factor-alpha, MESH: Time Factors, Immunity, Models, Immunological, Bystander Effect, Listeria monocytogenes, MESH: Tumor Necrosis Factor-alpha, Mutation, biology.protein, Immunization, Reactive Oxygen Species, MESH: Female, Immunologic Memory, CD8, 030215 immunology
Abstract: Cytolysis, interferon γ and tumor necrosis factor (TNF) α secretion are major effector mechanisms of memory CD8+ T cells that are believed to be required for immunological protection in vivo. By using mutants of the intracellular bacterium Listeria monocytogenes, we found that none of these effector activities is sufficient to protect against secondary infection with wild-type (WT) bacteria. We demonstrated that CCL3 derived from reactivated memory CD8+ T cells is required for efficient killing of WT bacteria. CCL3 induces a rapid TNF-α secretion by innate inflammatory mononuclear phagocytic cells (MPCs), which further promotes the production of radical oxygen intermediates (ROIs) by both MPCs and neutrophils. ROI generation is the final bactericidal mechanism involved in L. monocytogenes clearance. These results therefore uncover two levels of regulation of the antibacterial secondary protective response: (a) an antigen-dependent phase in which memory CD8+ T cells are reactivated and control the activation of the innate immune system, and (b) an antigen-independent phase in which the MPCs coordinate innate immunity and promote the bactericidal effector activities. In this context, CCL3-secreting memory CD8+ T cells are able to mediate “bystander” killing of an unrelated pathogen upon antigen-specific reactivation, a mechanism that may be important for the design of therapeutic vaccines.
Published: 2007
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46. Homeostasis of T cell numbers: from thymus production to peripheral compartmentalization and the indexation of regulatory T cells

Author: Benedita Rocha, Antonio A. Freitas, Afonso R. M. Almeida, Corine Tanchot, Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Differenciation Thymique et Physiologie des Lymphocytes T (U591), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Lymphocyte Count, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, T-Lymphocytes, Immunology, Population, Cell, Thymus Gland, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Antigen, medicine, Immunology and Allergy, Animals, Homeostasis, Humans, MESH: Animals, IL-2 receptor, Lymphocyte Count, education, MESH: Mice, 030304 developmental biology, 0303 health sciences, education.field_of_study, MESH: Humans, MESH: Thymus Gland, MESH: Gene Expression Regulation, Cell biology, medicine.anatomical_structure, MESH: T-Lymphocytes, Gene Expression Regulation, MESH: Homeostasis, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Memory T cell, Immunologic Memory, 030215 immunology
Abstract: A system under homeostatic control tends to maintain its structure and functions by establishing dynamic equilibriums controlled by multiple regulatory mechanisms. We have shown that this is the case for immune system. Several different mechanisms seem to participate in the homeostatic control of T cell numbers and population distribution. In other words, besides a quantitative dimension, there is also a qualitative dimension in T cell homeostasis. This is achieved through competition by driving the specialization of sub-populations of lymphocytes to occupy specific niches in the peripheral pool and by developing independent homeostatic mechanisms for each particular cell sub-set. Thus, the sizes of the naive and memory T cell compartments are governed by independent homeostatic mechanisms, which preserve the capacity to deal with any novel infection (conferred by the presence of naive T cells) whilst ensuring the efficacy of memory responses when dealing with recurring antigens. Peripheral T cell homeostasis also depends on the integrity of sub-population structure and the presence of regulatory CD4+ CD25+ T cells. The indexation of regulatory CD4+ CD25+ T cell numbers to the numbers of peripheral activated CD4+ T cells is another mechanism of homeostasis that has major advantages in the control of immune responses. It ensures continuous regulation of T cell numbers throughout immune responses, allowing for increases in cell numbers as long as the proportion of CD4+ CD25+ regulatory T cells is kept.
Published: 2007
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47. Maintenance of HIV-specific central and effector memory CD4 and CD8 T cells requires antigen persistence

Author: Gennady Bocharov, Urban Sester, Hans Köhler, Barbara Gärtner, Martina Sester, Hans W. Pees, Andreas Meyerhans, Simon Wain-Hobson, Biologie et Gestion des Adventices ( BGA ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), Rétrovirologie Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Biologie et Gestion des Adventices (BGA), Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: CD4-Positive T-Lymphocytes, Cytotoxic, T-Lymphocytes, Cytomegalovirus, HIV Infections, MESH : Viral Load, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, MESH: Antiretroviral Therapy, Highly Active, MESH: HIV-1, 0302 clinical medicine, T-Lymphocyte Subsets, Antiretroviral Therapy, Highly Active, Cytotoxic T cell, 0303 health sciences, biology, MESH: Kinetics, Effector, virus diseases, MESH: CD4-Positive T-Lymphocytes, MESH: HIV Infections, Viral Load, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Infectious Diseases, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, Lentivirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Immunologic Memory, MESH : Kinetics, MESH: Viral Load, MESH : HIV-1, MESH: Cytomegalovirus, MESH : Immunologic Memory, T cell, Immunology, Antiretroviral Therapy, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : T-Lymphocytes, Cytotoxic, MESH : Cytomegalovirus, 03 medical and health sciences, Antigen, Virology, medicine, MESH : HIV Infections, Humans, Highly Active, 030304 developmental biology, MESH: Humans, MESH : Humans, T lymphocyte, biology.organism_classification, MESH : Antiretroviral Therapy, Highly Active, MESH : T-Lymphocyte Subsets, Kinetics, HIV-1, Memory T cell, Immunologic Memory, MESH: T-Lymphocytes, Cytotoxic, CD8, T-Lymphocytes, Cytotoxic, 030215 immunology
Abstract: International audience; The HIV-specific central and effector CD4 and CD8 memory T cell populations disappear from the peripheral blood of infected individuals under highly active antiretroviral therapy (HAART) with a mean half-life of 6.0 and 7.7 months, respectively. By contrast, cytomegalovirus (CMV)-specific responses are stable or increase. The striking quantitative differences between T cell memory to two persistent viral infections are instructive as to how antigen dosage contributes to the maintenance of antigen-specific memory T cell responses in humans.
Published: 2007
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48. Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma

Author: Pierre Chambon, Ivan Dzhagalov, You-Wen He, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Toussaint, Jean-Luc, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Cell Differentiation, MESH: Inflammation, medicine.drug_class, Receptors, Retinoic Acid, Lymphocyte, medicine.medical_treatment, Immunology, Retinoic acid, Immune receptor, Biology, CD8-Positive T-Lymphocytes, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Listeria monocytogenes, chemistry.chemical_compound, Mice, Immune system, MESH: B-Lymphocytes, medicine, Immunology and Allergy, Animals, Listeriosis, MESH: Animals, Retinoid, Receptor, Vitamin A, MESH: Mice, Cells, Cultured, MESH: Vitamin A, Inflammation, MESH: Receptors, Retinoic Acid, B-Lymphocytes, MESH: Cytokines, Macrophages, MESH: Macrophages, Cell Differentiation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Listeria monocytogenes, MESH: CD8-Positive T-Lymphocytes, Cell biology, Retinoic acid receptor, medicine.anatomical_structure, Cytokine, chemistry, MESH: Immunologic Memory, Cytokines, Immunologic Memory, MESH: Listeria Infections, MESH: Cells, Cultured
Abstract: Vitamin A and its derivatives regulate a broad array of immune functions. The effects of these retinoids are mediated through members of retinoic acid receptors (RARs) and retinoid X receptors. However, the role of individual retinoid receptors in the pleiotropic effects of retinoids remains unclear. To dissect the role of these receptors in the immune system, we analyzed immune cell development and function in mice conditionally lacking RARγ, the third member of the RAR family. We show that RARγ is dispensable for T and B lymphocyte development, the humoral immune response to a T-dependent Ag and in vitro Th cell differentiation. However, RARγ-deficient mice had a defective primary and memory CD8+ T cell response to Listeria monocytogenes infection. Unexpectedly, RARγ-deficient macrophages exhibited impaired inflammatory cytokine production upon TLR stimulation. These results suggest that under physiological condition, RARγ is a positive regulator of inflammatory cytokine production.
Published: 2007

49. Cytosolic expression of SecA2 is a prerequisite for long-term protective immunity

Author: Grégoire Lauvau, Eric Muraille, Laurel L. Lenz, Pierre Gounon, Emilie Narni-Mancinelli, Nicolas Glaichenhaus, Delphine Bassand, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Integrated Department of Immunology, and University of Colorado [Boulder]
Subjects: MESH: Spleen, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, medicine.disease_cause, MESH: Listeria monocytogenes, Mice, 0302 clinical medicine, Cytosol, MESH: Cytosol, T-Lymphocyte Subsets, MESH: Animals, Listeriosis, MESH: Bacterial Proteins, Adenosine Triphosphatases, 0303 health sciences, Mice, Inbred BALB C, Host cell cytosol, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Cell biology, Liver, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Listeria Infections, MESH: Mutation, Secondary infection, Immunology, MESH: Mice, Inbred BALB C, Biology, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Bacterial Proteins, Immunity, Virology, medicine, MESH: Adenosine Triphosphatases, Animals, MESH: Mice, 030304 developmental biology, Pathogenic bacteria, Cytolysis, Mutation, Immunologic Memory, CD8, Spleen, 030215 immunology, MESH: Liver
Abstract: Induction of efficient adaptive T cell-mediated immunity against the intracellular bacterium Listeria monocytogenes requires its successful invasion of host cell cytosol. However, it is not clear whether its cytosolic escape and growth are sufficient to induce T cell-mediated clearance and protection upon secondary infection. To investigate this issue, we have searched for mutants that do not induce long-term protective immunity yet invade the cytosol of infected cells. We found that mice immunized with L. monocytogenes lacking the SecA2 ATPase, an auxiliary protein secretion system present in several Gram-positive pathogenic bacteria, mounted a robust cytolytic IFN-gamma-secreting CD8+ T cell response but were not protected against a secondary challenge with wild-type (wt) bacteria. Furthermore, CD8+ T cells from mice immunized with secA2- bacteria failed to transfer protection when injected into recipient mice demonstrating that they were unable to confer protection. Also, secA2- and wt L. monocytogenes spread to the same myeloid-derived cell types in vivo and SecA2 deficiency does not interfere with intracytosolic bacteria multiplication. Therefore, cytosol invasion is not sufficient for inducing secondary protective responses and induction of memory CD8+ T cells mediating long-term antibacterial protective immunity is dependent upon SecA2 expression inside the cytosol of host cells in vivo.
Published: 2007
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50. IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation

Author: Matthew L. Albert, Hélène Saklani, Robert B. Darnell, Deborah Braun, Heather K Morris, Nathalie E. Blachere, James P. Di Santo, Rockefeller University [New York], Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines et Développement Lymphoïde, Laboratory of Molecular Neuro-oncology, Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York], This work was supported by Pasteur Foundation (to N.E.B.), Howard Hughes Medical Institute (to N.E.B. and R.B.D.), La Fondation pour la Recherche Médicale (to D.B.), The Ligue Nationale Contre le Cancer, and European Young Investigator Awards scheme, European Science Foundation (to M.L.A.)., and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, MESH: 3T3 Cells, CD8-Positive T-Lymphocytes, Lymphocyte Activation, MESH: Mice, Knockout, Mice, 0302 clinical medicine, MESH: Receptors, Interleukin-12, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, Antigens, Viral, Cells, Cultured, Mice, Knockout, 0303 health sciences, Mice, Inbred BALB C, MESH: Dendritic Cells, Receptors, Interleukin-12, CD28, Cross-presentation, Cell Differentiation, 3T3 Cells, T-Lymphocytes, Helper-Inducer, MESH: CD8-Positive T-Lymphocytes, Cell biology, medicine.anatomical_structure, Influenza A virus, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Viral, MESH: Cells, Cultured, Signal Transduction, MESH: Cell Differentiation, MESH: Cross-Priming, MESH: Interferon-gamma, T cell, Immunology, MESH: Influenza A virus, MESH: Mice, Inbred BALB C, Biology, MESH: Antigens, CD40, 03 medical and health sciences, Interferon-gamma, Cross-Priming, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: T-Lymphocytes, Helper-Inducer, CD40 Antigens, Antigen-presenting cell, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, CD40, MESH: Interleukin-2, Dendritic Cells, Receptors, Interleukin, MESH: Receptors, Interleukin, Mice, Inbred C57BL, biology.protein, Interleukin-2, Immunologic Memory, CD8, 030215 immunology
Abstract: Dendritic cells (DCs) are capable of capturing exogenous Ag for the generation of MHC class I/peptide complexes. For efficient activation of memory CD8+ T cells to occur via a cross-presentation pathway, DCs must receive helper signals from CD4+ T cells. Using an in vitro system that reflects physiologic recall memory responses, we have evaluated signals that influence helper-dependent cross-priming, while focusing on the source and cellular target of such effector molecules. Concerning the interaction between CD4+ T cells and DCs, we tested the hypothesis that CD40 engagement on DCs is critical for IL-12p70 (IL-12) production and subsequent stimulation of IFN-γ release by CD8+ T cells. Although CD40 engagement on DCs, or addition of exogenous IL-12 are both sufficient to overcome the lack of help, neither is essential. We next evaluated cytokines and chemokines produced during CD4+ T cell/DC cross talk and observed high levels of IL-2 produced within the first 18–24 h of Ag-specific T cell engagement. Functional studies using blocking Abs to CD25 completely abrogated IFN-γ production by the CD8+ T cells. Although required, addition of exogenous IL-2 did not itself confer signals sufficient to overcome the lack of CD4+ T cell help. Thus, these data support a combined role for Ag-specific, cognate interactions at the CD4+ T cell/DC as well as the DC/CD8+ T cell interface, with the helper effect mediated by soluble noncognate signals.
Published: 2006
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