IL-15 Receptor Maintains Lymphoid Homeostasis by Supporting Lymphocyte Homing and Proliferation

The IL-15 receptor alpha subunit (IL-15Rα) mediates high-affinity binding of IL-15, a pleiotropic cytokine implicated in the development of innate immune cells. We have generated IL-15Rα null ( IL-15Rα −/− ) mice to understand the role of IL-15Rα in immune development and function. IL-15Rα −/− mice are markedly lymphopenic despite grossly normal T and B lymphocyte development. This lymphopenia is due to decreased proliferation and decreased homing of IL-15Rα −/− lymphocytes to peripheral lymph nodes. These mice are also deficient in natural killer cells, natural killer T cells, CD8 + T lymphocytes, and TCRγδ intraepithelial lymphocytes. In addition, memory phenotype CD8 + T cells are selectively reduced in number. Thus, IL-15Rα has pleiotropic roles in immune development and function, including the positive maintenance of lymphocyte homeostasis.