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PMID:10704459
| Citation |
Kennedy, MK, Glaccum, M, Brown, SN, Butz, EA, Viney, JL, Embers, M, Matsuki, N, Charrier, K, Sedger, L, Willis, CR, Brasel, K, Morrissey, PJ, Stocking, K, Schuh, JC, Joyce, S and Peschon, JJ (2000) Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J. Exp. Med. 191:771-80 |
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| Abstract |
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. |
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| Keywords |
Animals; CD8-Positive T-Lymphocytes/immunology; Cell Lineage; Epithelial Cells/immunology; Female; Immunologic Memory; Interleukin-15/genetics; Interleukin-15/immunology; Killer Cells, Natural/immunology; Lymph Nodes/anatomy & histology; Lymph Nodes/immunology; Lymphocyte Count; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Organ Size; Receptors, Interleukin-15; Receptors, Interleukin-2/genetics; Receptors, Interleukin-2/immunology; Spleen/anatomy & histology; Spleen/immunology; Thymus Gland/anatomy & histology; Thymus Gland/immunology; Vaccinia/mortality |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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