IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation

Abstract

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.