1. Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice
- Author
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Sylvie Darche, Hergen Spits, James P. Di Santo, Helene Strick-Marchand, Silvia Lopez-Lastra, Yan Li, Guillemette Masse-Ranson, Olivier Schwartz, Maud Boussand, Mathilde Dusséaux, Yves Levy, Antoine Toubert, Timothée Bruel, Oriane Fiquet, Erwan Corcuff, Mireille Centlivre, Nicolas Legrand, Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), 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), Service d'immunologie clinique et maladies infectieuses [Créteil], Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Supported by grants from the Institut Pasteur, INSERM, Gates Foundation (Grand Challenges in Global Health, J.P.D.), Agence Nationale de la Recherche (ANR) programme RPIB (Im_HIS, J.P.D.), the Laboratoire d'Excellence REVIVE (ANR‐10‐LABX‐73, J.P.D.), the Laboratoire d'Excellence Vaccine Research Institute (ANR‐10‐LABX‐77, Y.L.), the Laboratoire d'Excellence Milieu Intérieur (ANR‐10‐LABX‐69, H.M.), the Laboratoire d'Excellence IBEID (ANR‐10‐LABX‐62, O.S.), the Agence Nationale de Recherche sur le SIDA et les hepatites virales (ANRS 15465, O.S.), the European Commission Seventh Framework Programme n°305578 (PathCO, J.P.D.), and Gilead Sciences (00397, O.S. and J.P.D.)., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 305578,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,PATHCO(2012), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Experimental Immunology, AGEM - Digestive immunity, and AII - Inflammatory diseases
- Subjects
MESH: Cell Differentiation ,MESH: Mice, Transgenic ,T-Lymphocytes ,Transgene ,T cell ,Immunology ,MESH: Mice, Inbred BALB C ,Mice, Transgenic ,Human leukocyte antigen ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Humanized mice ,MESH: B-Lymphocytes ,MESH: HLA-A2 Antigen ,HLA-A2 Antigen ,medicine ,Animals ,Humans ,Immunology and Allergy ,MESH: Animals ,HLA-DR2 Antigen ,MESH: Mice ,030304 developmental biology ,B-Lymphocytes ,Mice, Inbred BALB C ,0303 health sciences ,MESH: Humans ,Lymphopoiesis ,Cell Differentiation ,MESH: Lymphopoiesis ,Animal models ,3. Good health ,Cell biology ,Disease Models, Animal ,MESH: HLA-DR2 Antigen ,Lymphocyte development ,MESH: T-Lymphocytes ,medicine.anatomical_structure ,Lymphatic system ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,MESH: Disease Models, Animal ,Stem cell ,CD8 ,030215 immunology - Abstract
International audience; Human immune system (HIS) mouse models provide a robust in vivo platform to study human immunity. Nevertheless, the signals that guide human lymphocyte differentiation in HIS mice remain poorly understood. Here, we have developed a novel Balb/c Rag2-/- Il2rg-/- SirpaNOD (BRGS) HIS mouse model expressing human HLA-A2 and -DR2 transgenes (BRGSA2DR2). When comparing BRGS and BRGSA2DR2 HIS mice engrafted with human CD34+ stem cells, a more rapid emergence of T cells in the circulation of hosts bearing human HLA was shown, which may reflect a more efficient human T-cell development in the mouse thymus. Development of CD4+ and CD8+ T cells was accelerated in BRGSA2DR2 HIS mice and generated more balanced B and T-cell compartments in peripheral lymphoid organs. Both B- and T-cell function appeared enhanced in the presence of human HLA transgenes with higher levels of class switched Ig, increased percentages of polyfunctional T cells and clear evidence for antigen-specific T-cell responses following immunization. Taken together, the presence of human HLA class I and II molecules can improve multiple aspects of human B- and T-cell homeostasis and function in the BRGS-based HIS mouse model.
- Published
- 2019