IL-15 trans-presentation promotes human NK cell development and differentiation in vivo
| Autor: | Yannick Jacques, Hergen Spits, James P. Di Santo, Nicholas D. Huntington, Nicolas Legrand, Kees Weijer, Erwan Corcuff, Erwan Mortier, Ariane Plet, Nuno L. Alves, Barbara Jaron |
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| Přispěvatelé: | Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation Immunitaire et Vaccinologie, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), 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), This work is supported by grants from Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Ligue National Contre le Cancer, National Health and Medical Research Council of Australia, The Menzies Foundation, and a Grand Challenges in Global Health grant from the Bill and Melinda Gates Foundation. Authors from the Institut Pasteur and Academic Medical Center are part of the Human Vaccine Consortium 'Grand Challenges in Global Health: Devise Reliable Testing Systems for New Vaccines:' (http://www.hv-consortium.org)., We acknowledge the Bloemenhove Clinic (Heemstede, The Netherlands) for providing fetal tissues. We would like to thank Allison Bordack, Dr. Jean-Jacques Mention, Dr. Ferenc Scheeren, Joran Volmer, and Jenny Meerding for reagents and technical assistance and Prof. Andreas Strasser for critiques on the manuscript., Other departments, AII - Amsterdam institute for Infection and Immunity, Cell Biology and Histology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Mortier, Erwan, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculteit der Geneeskunde |
| Rok vydání: | 2009 |
| Předmět: |
Cellular differentiation
[SDV]Life Sciences [q-bio] Mice Interleukin 21 0302 clinical medicine Transduction Genetic Immunology and Allergy Cytotoxic T cell Interleukin-15 Mice Knockout Mice Inbred BALB C 0303 health sciences Receptors Interleukin-15 Hematopoietic Stem Cell Transplantation Cell Differentiation hemic and immune systems Cell biology DNA-Binding Proteins Killer Cells Natural [SDV] Life Sciences [q-bio] Interleukin 15 Interleukin 12 [SDV.IMM]Life Sciences [q-bio]/Immunology Stem cell Interleukin Receptor Common gamma Subunit [SDV.IMM] Life Sciences [q-bio]/Immunology Cell Survival Lymphoid Tissue Recombinant Fusion Proteins Transplantation Heterologous Immunology bcl-X Protein Mice Nude chemical and pharmacologic phenomena Biology CD16 03 medical and health sciences Animals Humans Cell Proliferation 030304 developmental biology Lymphokine-activated killer cell Brief Definitive Report Hematopoietic Stem Cells Antigens Differentiation Mice Inbred C57BL Retroviridae Animals Newborn Brief Definitive Reports 030215 immunology |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2009, 206 (1), pp.25-34. ⟨10.1084/jem.20082013⟩ Journal of experimental medicine, 206(1), 25-34. Rockefeller University Press Journal of Experimental Medicine, 2009, 206 (1), pp.25-34. ⟨10.1084/jem.20082013⟩ Journal of Experimental Medicine, 206(1), 25-34. Rockefeller University Press The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20082013⟩ |
| Popis: | The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self-major histocompatibility complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2(-/-)gamma c(-/-) mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15 receptor alpha (IL-15R alpha) significantly augmented human NK cells. IL-15-IL-15R alpha complexes induced extensive NK cell proliferation and differentiation, resulting in accumulation of CD16(+)KIR(+) NK cells, which was not uniquely dependent on enhanced survival or preferential responsiveness of this subset to IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a linear fashion from CD56(hi)CD16(-)KIR(-) to CD56(lo)CD16(+)KIR(-), and finally to CD56(lo)CD16(+)KIR(+). These data provide the first evidence that IL-15 trans-presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists generates a robust humanized immune system model to study human NK cells in vivo. IL-15 receptor agonists may provide therapeutic tools to improve NK cell reconstitution after bone marrow transplants, enhance graft versus leukemia effects, and increase the pool of IL-15-responsive cells during immunotherapy strategies. |
| Databáze: | OpenAIRE |
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