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6 results on '"MESH : Immunophenotyping"'

1. In Untreated HIV-1–Infected Children, PBMC-Associated HIV DNA Levels and Cell-Free HIV RNA Levels Are Correlated to Distinct T-lymphocyte Populations

Author

Céline Didier, Christine Rouzioux, Stéphane Blanche, Marianne Burgard, Daniel Scott-Algara, Yves Rivière, Florence Buseyne, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Immunopathologie Virale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by Pasteur Institute, Agence Nationale de Recherches sur le SIDA et les hépatites virales, Sidaction, and the Paediatric AIDS Foundation., Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker - Enfants Malades - Université Paris Descartes - Paris 5 (UPD5), Service d'immunologie, hématologie, Centre National de la Recherche Scientifique (CNRS) - Institut Pasteur [Paris], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
HIV Infections, MESH: Flow Cytometry, CD8-Positive T-Lymphocytes, MESH: CD4-Positive T-Lymphocytes/virology, Polymerase Chain Reaction, MESH: DNA, Viral/immunology, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Immunopathology, Pharmacology (medical), Child, MESH : RNA, Viral/immunology, 0303 health sciences, MESH: DNA, Viral/blood, MESH: RNA, Viral/blood, virus diseases, MESH : Infant, Flow Cytometry, MESH: HIV Infections/virology, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Infant, 3. Good health, MESH : CD4-Positive T-Lymphocytes/virology, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: CD8-Positive T-Lymphocytes/immunology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Lentivirus, HIV RNA, MESH : HIV-1/immunology, HIV-specific T lymphocytes, Human leukocyte antigen, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Statistics, Nonparametric, MESH: CD4-Positive T-Lymphocytes/immunology, 03 medical and health sciences, MESH : Adolescent, MESH : HIV Infections/virology, Humans, MESH : CD8-Positive T-Lymphocytes/virology, MESH : DNA, Viral/genetics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Leukocytes, Mononuclear/virology, Perinatal HIV infection, MESH: Adolescent, MESH: HIV-1/immunology, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, RNA, MESH: Polymerase Chain Reaction, MESH: HIV Infections/immunology, medicine.disease, Virology, MESH: T-Lymphocyte Subsets/virology, MESH: Leukocytes, Mononuclear/immunology, MESH : CD4-Positive T-Lymphocytes/immunology, DNA, Viral, Immunology, HIV-1, Leukocytes, Mononuclear, MESH : RNA, Viral/genetics, MESH: Female, CD4-Positive T-Lymphocytes, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH : Leukocytes, Mononuclear/immunology, MESH : Child, Preschool, [ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH : HIV Infections/immunology, MESH: DNA, Viral/genetics, MESH : RNA, Viral/blood, MESH : Female, 030212 general & internal medicine, MESH : Polymerase Chain Reaction, MESH : T-Lymphocyte Subsets/virology, MESH: Statistics, Nonparametric, biology, MESH : HIV-1/genetics, MESH: Enzyme-Linked Immunosorbent Assay, MESH: CD8-Positive T-Lymphocytes/virology, Infectious Diseases, MESH : DNA, Viral/immunology, MESH : Immunophenotyping, RNA, Viral, Female, MESH: Leukocytes, Mononuclear/virology, MESH: RNA, Viral/genetics, MESH : DNA, Viral/blood, Adolescent, MESH: Immunophenotyping, MESH : Flow Cytometry, Enzyme-Linked Immunosorbent Assay, Virus, Immunophenotyping, HIV DNA, Acquired immunodeficiency syndrome (AIDS), MESH: T-Lymphocyte Subsets/immunology, medicine, immune activation, MESH : CD8-Positive T-Lymphocytes/immunology, MESH : Statistics, Nonparametric, MESH: RNA, Viral/immunology, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: HIV-1/genetics, T lymphocyte, biology.organism_classification, MESH : T-Lymphocyte Subsets/immunology, CD8
Abstract

International audience; Background: Clinical studies support biologically independent roles of cell-free HIV particles and HIV-infected cells in disease progression. The associations between the level of infected cells and immune markers have been poorly studied, particularly in perinatally infected children. Objective: We tested the hypothesis that independent roles of cell-free virus and infected cells in HIV pathogenesis should be revealed by different associations between each of them and specific immune markers. Methods: Levels of HIV RNA and DNA, HIV-specific CD8 T lymphocytes, activated and naïve/memory T lymphocytes were determined in 44 untreated HIV-1-infected children. Pearson’s partial correlation coefficients were used to assess associations between the variables. Results: Here we provide new information, by showing a direct correlation between the percentages of CD4+HLA-DR+ lymphocytes and HIV DNA levels. Furthermore, higher HIV-specific CD8 T lymphocyte frequencies were associated with lower HIV DNA levels. In contrast, CD8+38+ lymphocytes and memory CD4 lymphocytes were correlated only to the HIV RNA level. All correlations were independent of age and CD4 depletion.Conclusion: Several immune markers were correlated to either the HIV RNA or the HIV DNA level, but never to both of them, supporting the concept that cell-free virus and infected cells play different roles in HIV-1 immunopathogenesis.

Published
2010
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2. In vitro effects of cyclosporine A and tacrolimus on regulatory T-cell proliferation and function

Author

Olivier Moralès, Nadira Delhem, Yvan de Launoit, Véronique Pancré, Céline Miroux, Filomena Conti, Khaldoun Ghazal, Samia Ben Othman, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire, Université Paris Descartes - Paris 5 (UPD5), Unité de Transplantation, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Mécanismes de tumorigenèse et thérapies ciblées, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centre de Recherche Saint-Antoine (CR Saint-Antoine)

Subjects
medicine.medical_treatment, MESH : Cytokines, Pharmacology, Lymphocyte Activation, T-Lymphocytes, Regulatory, MESH: Cyclosporine, chemistry.chemical_compound, MESH : Phosphorylation, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Phosphorylation, MESH : Immunosuppressive Agents, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Cytokines, hemic and immune systems, 3. Good health, Cytokine, medicine.anatomical_structure, MESH : Calcineurin, 030220 oncology & carcinogenesis, MESH : Immunophenotyping, Cyclosporine, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Calcineurin, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, MESH: Cells, Cultured, Interleukin 2, MESH: Liver Transplantation, MESH: Immunophenotyping, Regulatory T cell, T cell, Calcineurin Inhibitors, NIM811, MESH: NFATC Transcription Factors, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Biology, Tacrolimus, Immunophenotyping, Proinflammatory cytokine, 03 medical and health sciences, MESH : Cyclosporine, MESH : Cells, Cultured, medicine, MESH: Tacrolimus, Humans, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, Transplantation, MESH: Humans, NFATC Transcription Factors, MESH: Phosphorylation, MESH : NFATC Transcription Factors, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH : Tacrolimus, Liver Transplantation, Calcineurin, chemistry, Immunology, MESH : Liver Transplantation
Abstract

International audience; BACKGROUND: Liver transplantation is the treatment of end-stage liver diseases, including hepatitis C. Immunosuppression prevents graft rejection but seems to accelerate the recurrence of hepatitis C. Regulatory T cells (Tregs) may be beneficial in tolerance but deleterious in recurrent hepatitis C. We evaluated the effects of cyclosporine or tacrolimus, the principal immunosuppressive drugs, on Treg proliferation and function. METHODS: Human Tregs were isolated from healthy donors and cultured with cyclosporine, tacrolimus, or NIM811, a cyclosporine analog devoid of calcineurin-inhibiting activity. Treg proliferation and suppressive activity were assessed. The phenotype, cytokine production, and phosphorylation profile of nuclear factor of activated T cell of Tregs were also analyzed. RESULTS: Cyclosporine and tacrolimus both decreased Treg proliferation, but only low doses of cyclosporine reduced Treg activity, by inducing the production of interleukin 2 proinflammatory cytokines in these cells. Moreover, NIM811 also inhibited Treg activity. The phosphorylation of nuclear factor of activated T cell in Tregs was not altered by cyclosporine, suggesting that the effects of this drug are independent of the calcineurin pathway. CONCLUSION: In summary, low doses of cyclosporine inhibit Treg activity, a finding that might explain the beneficial effect of this drug on hepatitis C recurrence. In contrast, by maintaining Treg activity, tacrolimus could be more helpful than cyclosporine in controlling rejection.

Published
2012
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3. High diversity of the immune repertoire in humanized NOD.SCID.gamma c-/- mice

Author

Marodon, Gilles, Desjardins, Delphine, Mercey, Laetitia, Baillou, Claude, Parent, Pierric, Manuel, Manuarii, Caux, Christophe, Bellier, Bertrand, Pasqual, Nicolas, Klatzmann, David, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), 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 Pierre et Marie Curie - Paris 6 (UPMC), Biologie et thérapeutique des pathologies immunitaires (BTPI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Unité d'hémato-oncologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Systématique, adaptation, évolution (SAE), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-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), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), 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 Pierre et Marie Curie - Paris 6 ( UPMC ), Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Systématique, adaptation, évolution ( SAE ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, MESH: Mice, Inbred NOD, MESH : Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Immunoglobulin Heavy Chains, MESH: Flow Cytometry, Hepacivirus, Mice, SCID, Polymerase Chain Reaction, MESH: Mice, Knockout, MESH : Hepacivirus, MESH: Animals, Newborn, Mice, Mice, Inbred NOD, MESH : Antigens, CD45, MESH : Female, MESH: Animals, MESH: Hepacivirus, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, MESH: Mice, SCID, MESH : Polymerase Chain Reaction, Mice, Knockout, Immunity, Cellular, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Animals, Newborn, Receptors, Antigen, T-Cell, gamma-delta, Flow Cytometry, MESH : Receptors, Antigen, T-Cell, gamma-delta, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Immunophenotyping, MESH: Immunization, Female, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Immunophenotyping, MESH : Flow Cytometry, MESH : Male, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Antigens, CD45, Immunophenotyping, MESH: Immunity, Cellular, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH : Mice, Animals, Humans, MESH: Mice, MESH : T-Lymphocytes, MESH: Humans, MESH : Mice, Inbred NOD, MESH : Humans, MESH: Clone Cells, MESH : Clone Cells, MESH : Immunity, Cellular, MESH: Polymerase Chain Reaction, MESH : Immunization, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH : Mice, SCID, MESH: Male, Clone Cells, MESH: T-Lymphocytes, Animals, Newborn, MESH : Mice, Knockout, Leukocyte Common Antigens, Immunization, MESH : Animals, MESH: Female, MESH: Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Abstract

International audience; The diversity of the human immune repertoire and how it relates to a functional immune response has not yet been studied in detail in humanized NOD.SCID.gammac(-/-) immunodeficient mice. Here, we used a multiplex PCR on genomic DNA to quantify the combinatorial diversity of all possible V-J rearrangements at the TCR-beta chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR-beta chain generated in the thymus was well preserved in the periphery, suggesting that human T cells were not vastly activated in mice, in agreement with phenotypic studies. We then show that the combinatorial diversity in NOD.SCID.gammac(-/-) mice reached 100% of human reference samples for both the TCR and the heavy chain of Ig. To document the functionality of this repertoire, we show that a detectable but weak HLA-restricted cellular immune response could be elicited in reconstituted mice after immunization with an adenoviral vector expressing HCV envelope glycoproteins. Altogether, our results suggest that humanized mice express a diversified repertoire and are able to mount antigen-specific immune responses.

Published
2009
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4. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+ T lymphocytes

Author

Dominique Cathelin, L. Arnould, Sylvain Audia, Christophe Ferrand, Nicolas Larmonier, Bernard Bonnotte, Bruno Chauffert, Marc Maynadié, Alexandra Nicolas, Eric Solary, A L Fanton, P. Foucher, Andrew Bateman, B. Lorcerie, E. Bergoin, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Department of Paediatrics, Steele Children's Research Centre, University of Arizona, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Cancer Sciences Division, University of Southampton [Southampton], Saas, Philippe, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), University of Arizona, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, University of Southampton, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Male, MESH: Combined Modality Therapy, Translational Studies, medicine.medical_treatment, MESH : Aged, MESH: Antineoplastic Agents, Alkylating, T-Lymphocytes, Regulatory, Immune tolerance, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, Immunophenotyping, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Antigens, CD45, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, IL-2 receptor, MESH : BCG Vaccine, Neoplasm Metastasis, MESH : Cyclophosphamide, MESH : Lymphocyte Count, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, MESH : Immune Tolerance, MESH : Reverse Transcriptase Polymerase Chain Reaction, FOXP3, Forkhead Transcription Factors, hemic and immune systems, Middle Aged, Combined Modality Therapy, 3. Good health, MESH : Forkhead Transcription Factors, MESH: BCG Vaccine, 030220 oncology & carcinogenesis, MESH : Immunophenotyping, MESH : Neoplasm Metastasis, BCG Vaccine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.drug, MESH: Lymphocyte Count, MESH: Immune Tolerance, Cyclophosphamide, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Immunophenotyping, MESH : Male, MESH : Antineoplastic Agents, Alkylating, Immunology, chemical and pharmacologic phenomena, MESH: Antigens, CD45, Metastatic carcinoma, 03 medical and health sciences, MESH: Forkhead Transcription Factors, medicine, Immune Tolerance, Humans, MESH : Middle Aged, Lymphocyte Count, Antineoplastic Agents, Alkylating, 030304 developmental biology, Aged, MESH: Humans, business.industry, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH: Cyclophosphamide, Immunotherapy, T lymphocyte, MESH: Neoplasm Metastasis, MESH: Male, Leukocyte Common Antigens, business, MESH : Combined Modality Therapy, MESH: Female
Abstract

SummaryWe determined the number and functional status of CD4+CD25high regulatory T cells (Treg) in blood samples from patients with metastatic carcinoma, and evaluated their sensitivity to a single intravenous infusion of cyclophosphamide. Treg numbers were significantly higher in 49 patients with metastatic cancer (9·2% of CD4+ T cells) compared to 24 healthy donors (7·1%). These cells expressed the transcription factor forkhead box P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) and intracellular CD152, and demonstrated a suppressive activity in vitro against CD4+CD25– autologous proliferation. At a single intravenous infusion, cyclophosphamide failed, in association with a non-specific immunotherapy by intratumoral bacille Calmette–Guérin (BCG), to modulate significantly Treg numbers or function. Metastatic cancer is associated with an expansion of peripheral blood CD4+CD25highFoxP3+GITR+CD152+Treg cells whose immunosuppressive properties do not differ from those of healthy subjects. Moreover, cyclophosphamide administration may not represent an optimal therapy to eliminate Treg, which further underlines the need to identify specific agents that would selectively deplete these cells.

Published
2007
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5. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127

Author

Benedita Rocha, Ana Cumano, Sophie Ezine, Erwan Corcuff, Lars Rogge, Marcos E. García-Ojeda, Odile Richard-Le Goff, Christian A. J. Vosshenrich, Sandrine I. Samson-Villeger, Delphine Guy-Grand, James P. Di Santo, Valérie Pasqualetto, Laurence Enault, Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), 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), Développement des Lymphocytes, Immunorégulation, 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Cytotoxicity, Immunologic, MESH: Signal Transduction, MESH : GATA3 Transcription Factor, MESH : Cytokines, MESH : Cytotoxicity, Immunologic, MESH : Interleukin-7 Receptor alpha Subunit, Interleukin 21, Mice, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, 0303 health sciences, MESH: Cytokines, MESH : Lymphocyte Subsets, MESH : Mice, Nude, Interleukin, virus diseases, Cell Differentiation, hemic and immune systems, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, Killer Cells, Natural, MESH : Immunophenotyping, Interleukin 12, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Killer Cells, Natural, MESH : Cell Differentiation, Signal Transduction, MESH : Interleukin-7, MESH: Cell Differentiation, MESH: Killer Cells, Natural, MESH: Immunophenotyping, MESH: Mice, Transgenic, Immunology, MESH: Lymphocyte Subsets, Mice, Nude, Mice, Transgenic, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, GATA3 Transcription Factor, Thymus Gland, Biology, CD16, Immunophenotyping, Interleukin-7 Receptor alpha Subunit, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH : Mice, MESH: GATA3 Transcription Factor, MESH: Mice, Nude, Animals, Humans, MESH : Thymus Gland, MESH: Cytotoxicity, Immunologic, MESH: Mice, 030304 developmental biology, MESH : Signal Transduction, Lymphokine-activated killer cell, MESH: Humans, Cell growth, Interleukin-7, MESH : Humans, MESH: Interleukin-7 Receptor alpha Subunit, MESH: Thymus Gland, Lymphocyte Subsets, MESH: Interleukin-7, Mice, Inbred C57BL, Myeloid-derived Suppressor Cell, MESH : Animals, 030215 immunology
Abstract

International audience; Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular markers of a pathway of mouse NK cell development that originates in the thymus. Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56(hi) CD16- NK cells, which we found expressed CD127 and had more GATA-3 expression than human CD56+ CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets.

Published
2006
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6. Human blood IgM 'memory' B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

Author

C.A. Reynaud, Mary Ellen Conley, Louis M. Staudt, Olivier Tournilhac, J.C. Weill, Jean-Laurent Casanova, Damien Bonnet, Andreas Rosenwald, Sandra K. Weller, Corinne Cordier, Bruce K. Tan, Gil Tchernia, Birte Steiniger, Alessandro Plebani, Moritz C. Braun, D S Kumararatne, 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), Metabolism Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-Center for Cancer Research-National Institutes of Health, 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), Department of Immunology, St Jude Children's Research Hospital-The University of Tennessee Health Science Center [Memphis] (UTHSC), Università degli Studi di Brescia [Brescia], Departments of Clinical Immunology and Medicine, Addenbrooke's Hospital, Service de cardiologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institute of Anatomy and Cell Biology, University of Marburg, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), National Cancer Institute ( NIH ) -Center for Cancer Research-National Institutes of Health, 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 ), St Jude Children's Research Hospital-University of Tennessee College of Medicine, Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Weller, Sandra, Università degli Studi di Brescia = University of Brescia (UniBs), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH: Spleen, MESH: Antigens, CD27, MESH : Aged, MESH : Child, Preschool, Biochemistry, Immunoglobulin D, 0302 clinical medicine, MESH : Child, immune system diseases, MESH: Autoimmune Diseases, MESH: Child, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Child, Gene Rearrangement, B-Lymphocyte, MESH: Aged, 0303 health sciences, B-Lymphocytes, MESH: Middle Aged, biology, MESH: Gene Rearrangement, B-Lymphocyte, MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Hematology, Middle Aged, MESH : Adult, Marginal zone, MESH: Infant, MESH: Immunoglobulin M, medicine.anatomical_structure, Child, Preschool, MESH : Immunophenotyping, Blood Circulation, MESH: Immunologic Memory, MESH: Complementarity Determining Regions, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Blood Circulation, Antibody, Adult, MESH : Spleen, MESH: Somatic Hypermutation, Immunoglobulin, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH: Immunophenotyping, MESH : Immunologic Memory, MESH : Immunoglobulin M, Immunology, MESH : Somatic Hypermutation, Immunoglobulin, Somatic hypermutation, MESH : Complementarity Determining Regions, Spleen, chemical and pharmacologic phenomena, Article, MESH : Immunoglobulin D, Autoimmune Diseases, Immunophenotyping, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Autoimmune Diseases, MESH : Antigens, CD27, MESH : Adolescent, MESH: B-Lymphocytes, medicine, Humans, MESH : Middle Aged, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Child, Preschool, Infant, MESH: Blood Circulation, MESH: Adult, Cell Biology, Gene rearrangement, Complementarity Determining Regions, Tumor Necrosis Factor Receptor Superfamily, Member 7, B-1 cell, Immunoglobulin M, MESH : Gene Rearrangement, B-Lymphocyte, biology.protein, Somatic Hypermutation, Immunoglobulin, Immunologic Memory, 030215 immunology
Abstract

International audience; The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM(+)IgD(+)CD27(+) cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria.

Published
2004
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