Reversible Defects in Natural Killer and Memory Cd8 T Cell Lineages in Interleukin 15–Deficient MiceMary K. Kennedy, Moira Glaccum, Sandra N. Brown, Eric A. Butz, Joanne L. Viney, Monica Embers, Naoto Matsuki, Keith Charrier, Lisa Sedger, Cynthia R. Willis, Kenneth Brasel, Philip J. Morrissey, Kim Stocking, JoAnn C. L. Schuh, Sebastian Joyce, Jacques J. Peschon
- Immunology and Allergy
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.