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5 results on '"MESH : Lymphopenia"'

1. Homeostasis of Peripheral CD4+ T Cells: IL-2Rα and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers

Author

Martine Papiernik, Afonso R. M. Almeida, Antonio A. Freitas, Nicolas Legrand, Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), 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 ), Other departments, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
CD4-Positive T-Lymphocytes, MESH: Adjuvants, Immunologic, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH : Radiation Chimera, Mice, Interleukin 21, 0302 clinical medicine, T-Lymphocyte Subsets, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Homeostasis, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH: Bone Marrow Transplantation, MESH : Lymphocyte Count, Bone Marrow Transplantation, Mice, Knockout, 0303 health sciences, MESH : Interphase, ZAP70, MESH: CD4-Positive T-Lymphocytes, CD28, Natural killer T cell, Cell biology, MESH: Homeostasis, MESH : CD4-Positive T-Lymphocytes, MESH : Homeostasis, Radiation Chimera, MESH: Survival Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Lymphopenia, MESH: Lymphocyte Count, MESH: Radiation Chimera, Immunology, MESH : Mice, Inbred C57BL, Biology, MESH : Interleukin-2, MESH: Receptors, Interleukin-2, MESH: Interphase, MESH: Lymphopenia, 03 medical and health sciences, Adjuvants, Immunologic, MESH: Mice, Inbred C57BL, MESH : Receptors, Interleukin-2, Lymphopenia, MESH : Mice, Animals, Lymphocyte Count, Antigen-presenting cell, Interphase, MESH: Mice, 030304 developmental biology, Interleukin 3, MESH : Bone Marrow Transplantation, Receptors, Interleukin-2, MESH: Interleukin-2, Survival Analysis, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, MESH : Adjuvants, Immunologic, MESH : Mice, Knockout, Interleukin-2, MESH : Animals, MESH : Survival Analysis, 030215 immunology
Abstract

We show that the lymphoid hyperplasia observed in IL-2Rα- and IL-2-deficient mice is due to the lack of a population of regulatory cells essential for CD4 T cell homeostasis. In chimeras reconstituted with bone marrow cells from IL-2Rα-deficient donors, restitution of a population of CD25+CD4+ T cells prevents the chaotic accumulation of lymphoid cells, and rescues the mice from autoimmune disease and death. The reintroduction of IL-2-producing cells in IL-2-deficient chimeras establishes a population of CD25+CD4+ T cells, and restores the peripheral lymphoid compartments to normal. The CD25+CD4+ T cells regulated selectively the number of naive CD4+ T cells transferred into T cell-deficient hosts. The CD25+CD4+/naive CD4 T cell ratio and the sequence of cell transfer determines the homeostatic plateau of CD4+ T cells. Overall, our findings demonstrate that IL-2Rα is an absolute requirement for the development of the regulatory CD25+CD4+ T cells that control peripheral CD4 T cell homeostasis, while IL-2 is required for establishing a sizeable population of these cells in the peripheral pools.

Published
2002

2. Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Author

E. Deconinck, Faezeh Legrand, Frédéric Grenouillet, Frédéric Dalle, Fabrice Larosa, Philippe Saas, Laurence Millon, Pierre Rohrlich, 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 ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), and Université de Bourgogne (UB)

Subjects
Male, medicine.medical_treatment, MESH : Cryptosporidium parvum, Cryptosporidiosis, Graft vs Host Disease, Hematopoietic stem cell transplantation, Azithromycin, Gastroenterology, 0302 clinical medicine, immune system diseases, MESH : Thiazoles, MESH: Animals, MESH : Female, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH : Azithromycin, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Antibacterial agent, 0303 health sciences, MESH: Middle Aged, biology, MESH : Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, MESH: Immunosuppression, Nitazoxanide, Immunosuppression, Hematology, Middle Aged, MESH : Adult, Nitro Compounds, MESH : Diagnosis, Differential, 3. Good health, Cryptosporidium parvum, surgical procedures, operative, MESH: Young Adult, Female, medicine.symptom, MESH : Lymphopenia, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Homologous, MESH : Male, MESH : Young Adult, MESH: Thiazoles, MESH: Graft vs Host Disease, Asymptomatic, MESH: Lymphopenia, Diagnosis, Differential, 03 medical and health sciences, Young Adult, MESH: Diagnosis, Differential, Internal medicine, MESH: Azithromycin, Lymphopenia, MESH : Hematopoietic Stem Cell Transplantation, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Cryptosporidiosis, MESH: Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy, Transplantation, MESH: Humans, 030306 microbiology, business.industry, MESH: Cryptosporidiosis, MESH : Humans, MESH: Adult, biology.organism_classification, MESH: Male, Thiazoles, Immunology, MESH : Immunosuppression, MESH: Cryptosporidium parvum, MESH : Animals, business, MESH: Female
Abstract

International audience; Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Published
2011

3. 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

4. Lymphocyte subsets in renal transplant recipients with de novo genitourinary malignancies

Author

J M Rebibou, Dominique Simula-Faivre, Philippe Saas, Hugues Bittard, Didier Ducloux, Jean Marc Chalopin, G. Guichard, Pierre Tiberghien, François Kleinclauss, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, 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 d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), 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 ), Saas, Philippe, Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC)

Subjects
CD4-Positive T-Lymphocytes, Male, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, 030232 urology & nephrology, MESH: T-Lymphocyte Subsets, 030230 surgery, Gastroenterology, MESH: Kidney Transplantation, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, T-Lymphocyte Subsets, Renal cell carcinoma, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Kidney transplantation, MESH: Aged, education.field_of_study, MESH: Middle Aged, Incidence (epidemiology), MESH: CD4-Positive T-Lymphocytes, MESH: Carcinoma, Renal Cell, Middle Aged, Kidney Neoplasms, 3. Good health, MESH: Urinary Bladder Neoplasms, MESH : Urinary Bladder Neoplasms, MESH : CD4-Positive T-Lymphocytes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Lymphopenia, MESH : Prostatic Neoplasms, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Urology, Population, MESH: Lymphopenia, 03 medical and health sciences, Lymphopenia, Internal medicine, medicine, Humans, MESH : Middle Aged, education, Carcinoma, Renal Cell, Dialysis, Aged, Retrospective Studies, MESH: Humans, business.industry, Genitourinary system, MESH : Humans, Prostatic Neoplasms, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, MESH : T-Lymphocyte Subsets, MESH : Kidney Neoplasms, MESH: Male, Urinary Bladder Neoplasms, MESH: Prostatic Neoplasms, Immunology, MESH : Kidney Transplantation, Skin cancer, Lymphocytopenia, MESH: Kidney Neoplasms, business, MESH: Female
Abstract

Introduction: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence. Patients and Methods: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry. Results and Conclusion: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR.

Published
2008

5. 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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