Reversible Defects in Natural Killer and Memory Cd8 T Cell Lineages in Interleukin 15–Deficient Mice
| Autor: | Kim L. Stocking, Sandra N. Brown, Sebastian Joyce, Philip J. Morrissey, Monica E. Embers, Naoto Matsuki, Keith Charrier, Eric A. Butz, Lisa M. Sedger, Kenneth Brasel, Moira Glaccum, Jacques J. Peschon, JoAnn C. L. Schuh, Joanne L. Viney, Mary K. Kennedy, Cynthia R. Willis |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_treatment Immunology Thymus Gland CD8-Positive T-Lymphocytes Biology Mice 03 medical and health sciences 0302 clinical medicine Immunophenotyping Vaccinia medicine Animals Immunology and Allergy Cytotoxic T cell Cell Lineage Lymphocyte Count 030304 developmental biology Interleukin-15 0303 health sciences Receptors Interleukin-15 Gene targeting Epithelial Cells Receptors Interleukin-2 Organ Size Mice Mutant Strains Killer Cells Natural Mice Inbred C57BL Cytokine Interleukin 15 Knockout mouse Commentary Intraepithelial lymphocyte Female Lymph Nodes Immunologic Memory Spleen CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.191.5.771 |
| Popis: | C57BL/6 mice genetically deficient in interleukin 15 (IL-15−/− mice) were generated by gene targeting. IL-15−/− mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8+ T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15−/− mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15−/− mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15−/− mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15−/− mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15−/− mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine. |
| Databáze: | OpenAIRE |
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