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8 results on '"MESH : Lymphocytes"'

1. Mechanisms of action of antithymocyte globulin: old dogs with new tricks!

Author

Béatrice Gaugler, Mohamad Mohty, Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], 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 ), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), and Saas, Philippe

Subjects
Cancer Research, [SDV.IMM] Life Sciences [q-bio]/Immunology, Globulin, medicine.medical_treatment, MESH : Lymphocytes, MESH : Antilymphocyte Serum, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, MESH: Antilymphocyte Serum, Antigen, Antigens, CD, MESH : Antigens, CD, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Lymphocytes, MESH: Antigens, CD, Antilymphocyte Serum, 030304 developmental biology, Immunosuppression Therapy, 0303 health sciences, MESH: Humans, MESH: Dendritic Cells, biology, MESH : Humans, MESH: Immunosuppression, Immunosuppression, T-cell depletion, Dendritic Cells, Hematology, 3. Good health, Transplantation, Oncology, Polyclonal antibodies, MESH : Dendritic Cells, MESH : Immunosuppression, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Lymphocytes, Antithymocyte globulins, 030215 immunology
Abstract

International audience; Understanding the mechanisms underlying immunological tolerance is the key to successful transplantation. Recent findings demonstrate that polyclonal antibodies such as the antithymocyte globulins preparations can provide wide spectrum immunomodulation, suggesting that their use in the immunosuppression therapeutic armamentarium may help in reducing the incidence of organ rejection and improving patients' outcome after hematopoietic stem cell transplantation.

Published
2008

2. Human Blood-Brain Barrier Disruption by Retroviral-Infected Lymphocytes: Role of Myosin Light Chain Kinase in Endothelial Tight-Junction Disorganization

Author

Marie-Christine Prévost, Christine Schmitt, Simona Ozden, Antoine Gessain, Babette B. Weksler, Pierre-Emmanuel Ceccaldi, Philippe V. Afonso, Pierre-Olivier Couraud, Ignacio A. Romero, Danielle Seilhean, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Microscopie électronique (Plate-forme), Institut Pasteur [Paris], CHU Pitié-Salpêtrière [APHP], Weill Medical College of Cornell University [New York], Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Department of Biological Sciences, The Open University [Milton Keynes] (OU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie, Hôpital de la Salpétrière, 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
Pathology, MESH : Cerebellum, [SDV]Life Sciences [q-bio], MESH : Lymphocytes, MESH : Herpesviridae Infections, MESH : Models, Immunological, MESH : Herpesvirus 8, Human, MESH : Blood-Brain Barrier, 0302 clinical medicine, Cerebellum, Interleukin-1alpha, Tropical spastic paraparesis, Immunology and Allergy, Lymphocytes, Transcellular, Cell Line, Transformed, MESH : Tumor Necrosis Factor-alpha, Human T-lymphotropic virus 1, 0303 health sciences, MESH : Neoplasm Recurrence, Local, Tight junction, MESH : Neurodegenerative Diseases, MESH : Cell Line, Transformed, Neurodegenerative Diseases, MESH : Human T-lymphotropic virus 1, Paraparesis, Tropical Spastic, 3. Good health, Cell biology, MESH : Pleural Effusion, Malignant, medicine.anatomical_structure, Spinal Cord, Blood-Brain Barrier, Paracellular transport, Infiltration (medical), medicine.medical_specialty, Myosin light-chain kinase, Endothelium, Immunology, MESH : Lymphoma, AIDS-Related, Biology, MESH : Myosin-Light-Chain Kinase, MESH : Lymphoma, Myosin light chain kinase activity, Tight Junctions, 03 medical and health sciences, medicine, Humans, MESH : Interleukin-1alpha, Myosin-Light-Chain Kinase, 030304 developmental biology, MESH : Tight Junctions, Tumor Necrosis Factor-alpha, MESH : Endothelial Cells, MESH : Humans, Models, Immunological, Endothelial Cells, Membrane Proteins, MESH : Spinal Cord, Phosphoproteins, medicine.disease, MESH : Paraparesis, Tropical Spastic, MESH : Endothelium, Vascular, MESH : Membrane Proteins, Zonula Occludens-1 Protein, Endothelium, Vascular, MESH : Phosphoproteins, 030217 neurology & neurosurgery
Abstract

The blood-brain barrier (BBB), which constitutes the interface between blood and cerebral parenchyma, has been shown to be disrupted during retroviral associated neuromyelopathies. Human T cell leukemia virus (HTLV-1)-associated myelopathy/tropical spastic paraparesis is a slowly progressive neurodegenerative disease, in which evidence of BBB breakdown has been demonstrated by the presence of lymphocytic infiltrates in the CNS and plasma protein leakage through cerebral endothelium. Using an in vitro human BBB model, we investigated the cellular and molecular mechanisms involved in endothelial changes induced by HTLV-1-infected lymphocytes. We demonstrate that coculture with infected lymphocytes induces an increase in paracellular endothelial permeability and transcellular migration, via IL-1α and TNF-α secretion. This disruption is associated with tight junction disorganization between endothelial cells, and alterations in the expression pattern of tight junction proteins such as zonula occludens 1. These changes could be prevented by inhibition of the NF-κB pathway or of myosin light chain kinase activity. Such disorganization was confirmed in histological sections of spinal cord from an HTLV-1-associated myelopathy/tropical spastic paraparesis patient. Based on this BBB model, the present data indicate that HTLV-1-infected lymphocytes can induce BBB breakdown and may be responsible for the CNS infiltration that occurs in the early steps of retroviral-associated neuromyelopathies.

Published
2007

3. Adipose-derived stromal cells: cytokine expression and immune cell contaminants

Author

Coralie Sengenès, Jean Galitzky, Pauline Decaunes, Anne Bouloumié, David Estève, Alexia Zakaroff-Girard, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Simon, Marie Francoise, Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), and Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Cytokines, MESH : Lymphocytes, Cell, Lipopolysaccharide Receptors, Adipose tissue, MESH : Adipocytes, MESH: Flow Cytometry, Antigens, CD34, Cell Separation, 030204 cardiovascular system & hematology, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, Adipocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Endothelial Cells, Lymphocytes, 0303 health sciences, MESH: Cytokines, biology, Chemistry, MESH: Antigens, CD14, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Cell Differentiation, Flow Cytometry, 3. Good health, Cell biology, Platelet Endothelial Cell Adhesion Molecule-1, medicine.anatomical_structure, Adipose Tissue, MESH : Antigens, CD31, MESH : Antigens, CD34, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Antibody, MESH : Cell Differentiation, MESH: Adipose Tissue, MESH: Cell Differentiation, Stromal cell, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Flow Cytometry, MESH : Adipose Tissue, MESH: Cell Separation, 03 medical and health sciences, Immune system, MESH: RNA, Lymph node stromal cell, medicine, Humans, Progenitor cell, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, MESH : Endothelial Cells, MESH : Humans, Cytokine expression, Endothelial Cells, MESH: Antigens, CD31, MESH: Antigens, CD34, MESH : Antigens, CD14, MESH : Stromal Cells, MESH : Cell Separation, Immunology, biology.protein, RNA, MESH: Lymphocytes, MESH: Stromal Cells, Stromal Cells
Abstract

International audience; The present method describes an immunoselection/depletion approach to isolate the native human adipose tissue-derived progenitor cells that are free from endothelial cells and immune cells by the use of magnetic nanobeads and microbeads coupled to antibodies. Moreover, methods to isolate and to analyse the distinct cell populations that constitute the microenvironment of the human adipose tissue progenitor cells, i.e. mature adipocytes, endothelial cells, and macrophages, are mentioned.

Published
2010

4. A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report

Author

Daniel Rabier, Silvia Napuri-Gouel, Annie Martin-Ponthieu, Michèle Brivet, Niels Gregersen, Monique Fontaine, Brage S. Andresen, Gilbert Briand, Karine Mention-Mulliez, Dries Dobbelaere, Christine Vianey-Saban, Ronald J.A. Wanders, Joseph Vamecq, Anne-Frédérique Dessein, David S. Millington, Laboratoire d'hormonologie, métabolisme-nutrition et oncologie (HMNO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Research Unit for Molecular Medicine, Aarhus University [Aarhus]-Institute of Clinical Medicine, Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Service de biochimie métabolique [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), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de neurologie pédiatrique, branche épilepsie, Centre de référence des maladies métaboliques héréditaires, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'application de Spectrométrie de Masse (LASM), Université de Lille, Droit et Santé, Department of Paediatrics, Duke University Medical Center, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Laboratory of Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), This work was supported by grants from the French Ministère de la Santé (PHRC 2003R/ 1903) and FMO (Fédération des Maladies Orphelines)., Aarhus University [Aarhus] - Institute of Clinical Medicine, UNIVERSITY OF SOUTHERN DENMARK, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Hôpital Jeanne de Flandre [Lille] - Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Academic Medical Center [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA) - University of Amsterdam [Amsterdam] (UvA), Faculteit der Geneeskunde, BMC, Ed., Amsterdam Gastroenterology Endocrinology Metabolism, and Laboratory Genetic Metabolic Diseases

Subjects
Male, MESH: Oxidation-Reduction, MESH : Lymphocytes, lcsh:Medicine, MESH : Carnitine, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, Compound heterozygosity, Polymerase Chain Reaction, Acyl-CoA Dehydrogenase, 0302 clinical medicine, Genetics(clinical), MESH : Female, Pharmacology (medical), Lymphocytes, MESH : Acyl-CoA Dehydrogenase, MESH : Polymerase Chain Reaction, MESH : Fatty Acids, Cells, Cultured, Genetics (clinical), Skin, Medicine(all), Genetics, 0303 health sciences, MESH: Carnitine, Fatty Acids, MESH: Genetic Predisposition to Disease, MESH: Acyl-CoA Dehydrogenase, General Medicine, MESH : Adult, Pedigree, MESH: Fatty Acids, 3. Good health, Child, Preschool, Mutation (genetic algorithm), Female, MESH : Mutation, Oxidation-Reduction, ACADM Gene, MESH: Cells, Cultured, medicine.drug, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Pedigree, MESH : Male, Biology, 03 medical and health sciences, MESH : Deficiency Diseases, MESH: Skin, Carnitine, Internal medicine, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Skin, medicine, Humans, Genetic Predisposition to Disease, ACADM, 030304 developmental biology, MESH : Oxidation-Reduction, [SDV.GEN]Life Sciences [q-bio]/Genetics, Newborn screening, MESH: Humans, Research, lcsh:R, MESH : Humans, MESH: Child, Preschool, Acyl CoA dehydrogenase, MESH: Adult, MESH: Polymerase Chain Reaction, Fibroblasts, MCADD, medicine.disease, MESH: Male, Endocrinology, MESH: Deficiency Diseases, MESH: Fibroblasts, MESH : Pedigree, Mutation, biology.protein, MESH : Genetic Predisposition to Disease, MESH: Lymphocytes, Deficiency Diseases, MESH: Female, 030217 neurology & neurosurgery
Abstract

A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.

Published
2010

5. Distinct effects of DNA-PKcs and Artemis inactivation on signal joint formation in vivo

Author

Evelyne Jouvin-Marche, Cédric Touvrey, Serge M. Candéias, Chrystelle Couedel, Jean-Pierre de Villartay, Maria Jasin, Pauline Soulas, Rachel Couderc, Patrice N. Marche, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developmental Biology Program, Memorial Sloane Kettering Cancer Center [New York], 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), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Memorial Sloan Kettering Cancer Center, 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 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 ), Laboratoire Lésions des Acides Nucléiques ( LAN ), Service de Chimie Inorganique et Biologique ( SCIB - UMR E3 ), Institut Nanosciences et Cryogénie ( INAC ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut Nanosciences et Cryogénie ( INAC ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Candéias, Serge, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), 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), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Protein kinase complex, MESH : Molecular Sequence Data, MESH : DNA, MESH : Lymphocytes, DNA-Activated Protein Kinase, Mice, SCID, MESH: Base Sequence, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Artemis, Mice, 0302 clinical medicine, MESH: Endonucleases, MESH : Antigens, Nuclear, MESH : Endonucleases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Lymphocytes, MESH: Mice, SCID, MESH : DNA-Activated Protein Kinase, DNA-PKcs, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, V(D)J recombination, MESH: DNA, Nuclear Proteins, Antigens, Nuclear, T cell receptor genes, Junctional diversity, DNA-Binding Proteins, Non-homologous end joining, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH: Enzyme Activation, [SDV.IMM] Life Sciences [q-bio]/Immunology, Molecular Sequence Data, Immunology, MESH : Mice, Inbred C57BL, 03 medical and health sciences, MESH: Mice, Inbred C57BL, signal joints, MESH : Mice, Animals, Protein kinase A, MESH: Antigens, Nuclear, MESH: Mice, Ku Autoantigen, Molecular Biology, 030304 developmental biology, Nuclease, MESH: Molecular Sequence Data, Base Sequence, MESH : Nuclear Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Endonucleases, Molecular biology, MESH : Mice, SCID, Enzyme Activation, Mice, Inbred C57BL, MESH: DNA-Activated Protein Kinase, biology.protein, MESH: Lymphocytes, MESH : Base Sequence, MESH : Animals, Homologous recombination, MESH : Enzyme Activation, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, 030217 neurology & neurosurgery
Abstract

International audience; The assembly of functional immune receptor genes via V(D)J recombination in developing lymphocytes generates DNA double-stranded breaks intermediates that are repaired by non-homologous end joining (NHEJ). This repair pathway requires the sequential recruitment and activation onto coding and signal DNA ends of several proteins, including the DNA-dependent protein kinase and the nuclease Artemis. Artemis activity, triggered by the DNA-dependent protein kinase, is necessary to process the genes hairpin-sealed coding ends but appears dispensable for the ligation of the reciprocal phosphorylated, blunt-ended signal ends into a signal joint. The DNA-dependent protein kinase is however present on signal ends and could potentially recruit and activate Artemis during signal joint formation. To determine whether Artemis plays a role during the resolution of signal ends during V(D)J recombination, we analyzed the structure of signal joints generated in developing thymocytes during the rearrangement of T cell receptor genes in wild type mice and mice mutated for NHEJ factors. These joints exhibit junctional diversity resulting from N nucleotide polymerization by the terminal nucleotidyl transferase and nucleotide loss from one or both of the signal ends before they are ligated. Our results show that Artemis participates in the repair of signal ends in vivo. Furthermore, our results also show that while the DNA-dependent protein kinase complex protects signal ends from processing, including deletions, Artemis seems on the opposite to promote their accessibility to modifying enzymes. In addition, these data suggest that Artemis might be the nuclease responsible for nucleotide loss from signal ends during the repair process.

Published
2008

6. Comparison of histopathologic-clinical characteristics of Jessner's lymphocytic infiltration of the skin and lupus erythematosus tumidus: Multicenter study of 46 cases

Author

Janine Wechsler, François Aubin, Marie-Claude Marguery, Pierre Thomas, D. Leroy, Henri Adamski, Daniel Lambert, Bernard Cribier, Valérie Rémy-Leroux, Fabienne Léonard, Philippe Bernard, Laboratoire de Modélisation du Matériel Electrique ( LAMEL ), Laboratoire d’Électrotechnique et d’Électronique de Puissance - EA 2697 ( L2EP ), Ecole Centrale de Lille-Haute Etude d'Ingénieurs-Université de Lille-Ecole Centrale de Lille-Haute Etude d'Ingénieurs-Université de Lille-EDF R&D ( EDF R&D ), EDF ( EDF ) -EDF ( EDF ), Service de dermatologie, Hôpital Pontchaillou, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Direction de la recherche, Société des accumulateurs fixes et de traction ( SAFT ), Laboratoire de Modélisation du Matériel Electrique (LAMEL), Laboratoire d’Électrotechnique et d’Électronique de Puissance - EA 2697 (L2EP), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Société des accumulateurs fixes et de traction (SAFT), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Électrotechnique et d’Électronique de Puissance - ULR 2697 (L2EP), Centrale Lille-Haute Etude d'Ingénieurs-Université de Lille-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Centrale Lille-Haute Etude d'Ingénieurs-Université de Lille-Arts et Métiers Sciences et Technologies, Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centrale Lille-Université de Lille-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Arts et Métiers Sciences et Technologies, Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-EDF R&D (EDF R&D), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC)

Subjects
Male, Pathology, MESH : Retrospective Studies, MESH : Lymphocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH : Female, Lymphocytes, Skin, Dermoepidermal junction, education.field_of_study, Univariate analysis, Systemic lupus erythematosus, MESH: Photosensitivity Disorders, MESH : Adult, 3. Good health, 030220 oncology & carcinogenesis, Phototesting, MESH: Lupus Erythematosus, Discoid, Female, MESH : Skin Diseases, Adult, medicine.medical_specialty, Ultraviolet Rays, MESH : Male, Population, MESH: Skin Diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Skin Diseases, Antimalarials, 03 medical and health sciences, Lupus Erythematosus, Discoid, MESH : Lupus Erythematosus, Discoid, MESH: Skin, medicine, MESH : Skin, Humans, Photosensitivity Disorders, education, Retrospective Studies, Lupus erythematosus, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Lupus Erythematosus Tumidus, MESH: Antimalarials, MESH: Male, MESH : Ultraviolet Rays, MESH : Photosensitivity Disorders, MESH : Antimalarials, Histopathology, MESH: Ultraviolet Rays, MESH: Lymphocytes, business, MESH: Female
Abstract

International audience; OBJECTIVE: We sought to identify criteria able to distinguish between Jessner's lymphocytic infiltration of the skin (JLIS) and lupus erythematosus tumidus (LET). METHODS: The following characteristics were recorded in a retrospective, multicenter analysis of patients with JLIS and LET: clinical features (number, size, type, and localization of lesions; photosensitivity; extracutaneous signs), histologic findings, phototesting, lupus serology, treatment, and outcome. Available histologic slides were reviewed blinded to the initial diagnosis using a pre-established grid. RESULTS: Univariate analysis of data from patients with JLIS (15 women, 17 men; mean age: 35 years) and LET (13 women, one man; mean age: 31 years) showed the following significant (P < .05) differences: more frequent back involvement and annular lesions in JLIS, as opposed to female predominance, more frequent face involvement, and plaques in LET. Phototesting, especially ultraviolet B, induced lesions in 18 of 26 patients with JLIS and all 4 with LET. The blinded histologic review (33 samples) only found slight epidermal atrophy and focal thickened dermoepidermal junction more frequent and perivascular lymphocyte infiltrations less dense in LET. The two groups of patients reclassified according histopathologic features (18 LET and 11 JLIS) showed only slight clinical differences (more frequent nasal bridge lesions in LET and annular lesions in JLIS). LIMITATION: The retrospective nature of the study is a limitation. CONCLUSION: JLIS and LET in this population showed more similarities than differences, supporting a continuous spectrum covering these two entities.

Published
2008

7. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes

Author

Ronald N. Germain, Frédéric Brau, Nicolas Glaichenhaus, Jackson G. Egen, Lily Koo, Marc Bajénoff, Jean Pierre Laugier, Lymphocyte Biology Section ( NIAID ), National Institutes of Health, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Commun de Microscopie Appliquée ( CCMA ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Intramural Research Program of NIAID, NIH, DHHS, Institut de la Santé et de la Recherche Médicale (INSERM), Lymphocyte Biology Section (NIAID), 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), Centre Commun de Microscopie Appliquée (CCMA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), and 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)

Subjects
Pathology, Adoptive cell transfer, Lymphocyte, MESH : Immunohistochemistry, MESH : Diagnostic Imaging, MESH : Lymphocytes, MESH: Chemotaxis, Leukocyte, MESH: Lymph Nodes, Cell Communication, Mice, 0302 clinical medicine, Reticular cell, MESH: Microscopy, Confocal, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Lymphocytes, MESH : Lymph Nodes, 0303 health sciences, Microscopy, Confocal, MESH : Adoptive Transfer, Cell migration, MESH : Chemotaxis, Leukocyte, Adoptive Transfer, Immunohistochemistry, Cell biology, Chemotaxis, Leukocyte, medicine.anatomical_structure, Infectious Diseases, MESH : Microscopy, Electron, Transmission, MESH: Microscopy, Electron, Transmission, [SDV.IMM]Life Sciences [q-bio]/Immunology, Diagnostic Imaging, MESH : Microscopy, Electron, Scanning, medicine.medical_specialty, Stromal cell, Naive T cell, MESH: Microscopy, Electron, Scanning, MESH : Cell Communication, T cell, Immunology, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, Microscopy, Electron, Transmission, MESH: Mice, Inbred C57BL, MESH: Cell Communication, MESH : Mice, medicine, Animals, MESH : Microscopy, Confocal, MESH: Mice, 030304 developmental biology, Follicular dendritic cells, MESH: Diagnostic Imaging, MESH: Immunohistochemistry, Mice, Inbred C57BL, MESH: Adoptive Transfer, CELLIMMUNO, MESH : Stromal Cells, Microscopy, Electron, Scanning, CELLBIO, MESH: Lymphocytes, Lymph Nodes, MESH : Animals, Stromal Cells, MESH: Stromal Cells, 030215 immunology
Abstract

SummaryAfter entry into lymph nodes (LNs), B cells migrate to follicles, whereas T cells remain in the paracortex, with each lymphocyte type showing apparently random migration within these distinct areas. Other than chemokines, the factors contributing to this spatial segregation and to the observed patterns of lymphocyte movement are poorly characterized. By combining confocal, electron, and intravital microscopy, we showed that the fibroblastic reticular cell network regulated naive T cell access to the paracortex and also supported and defined the limits of T cell movement within this domain, whereas a distinct follicular dendritic cell network similarly served as the substratum for movement of follicular B cells. These results highlight the central role of stromal microanatomy in orchestrating cell migration within the LN.

Published
2006

8. Familial NK cell deficiency associated with impaired IL-2- and IL-15-dependent survival of lymphocytes

Author

Jean-Jacques Mention, Jean-Laurent Casanova, Emmanuelle Jouanguy, Laure Gineau, Alexandre Alcaïs, Jean-Claude Carel, Anne Puel, Celine Eidenschenk, Françoise Le Deist, Eric Vivier, Benoit Pasquier, Ingrid M. Fleckenstein, Haon, Marie Laure, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), 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 ), 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), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Lymphocyte, MESH : Lymphocytes, MESH: Interleukin-15, Apoptosis, MESH : Child, Preschool, Interleukin 21, MESH : Child, MESH: Child, Immunology and Allergy, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, IL-2 receptor, Lymphocytes, Child, Interleukin-15, MESH : Cell Survival, MESH : Infant, MESH: Infant, MESH: Case-Control Studies, Killer Cells, Natural, medicine.anatomical_structure, MESH: Cell Survival, Interleukin 15, Child, Preschool, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Killer Cells, Natural, MESH : Lymphopenia, MESH: Killer Cells, Natural, MESH : Case-Control Studies, MESH: Immunologic Deficiency Syndromes, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cell Survival, T cell, Immunology, MESH : Interleukin-15, Biology, MESH : Family Health, MESH : Interleukin-2, MESH: Lymphopenia, MESH : Adolescent, Lymphopenia, medicine, Humans, MESH: Adolescent, Family Health, MESH: Humans, MESH: Apoptosis, MESH: Child, Preschool, MESH : Humans, Immunologic Deficiency Syndromes, Infant, MESH: Interleukin-2, MESH : Immunologic Deficiency Syndromes, Case-Control Studies, MESH: Family Health, Interleukin-2, MESH: Lymphocytes, MESH: Female, CD8, MESH : Apoptosis
Abstract

We previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient CD8 αβ T lymphopenia and a persistent lack of blood NK cells. We describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-transformed T cells, in the surviving child. Clearly, NK cells could not be studied. However, peripheral blood T lymphocytes displayed excessive apoptosis ex vivo. Moreover, the survival rates of CD4 and CD8 αβ T cell blasts generated in vitro, and herpesvirus saimiri-transformed T cells cultured in vitro, were low, but not nil, following treatment with IL-2 and IL-15. In contrast, Fas-mediated activation-induced cell death was not enhanced, indicating a selective excess of cytokine deprivation-mediated apoptosis. In keeping with the known roles of IL-2 and IL-15 in the development of NK and CD8 T cells in the mouse model, these data suggest that an impaired, but not abolished, survival response to IL-2 and IL-15 accounts for the persistent lack of NK cells and the transient CD8 αβ T lymphopenia documented in vivo. Impaired cytokine-mediated lymphocyte survival is likely to be the pathogenic mechanism underlying this novel form of inherited and selective NK deficiency in humans.

Published
2006

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