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

The IL-15 receptor alpha subunit (IL-15R alpha) mediates high-affinity bind ing of IL-15, a pleiotropic cytokine implicated in the development of innat e immune cells. We have generated IL-15R alpha null (IL-15R alpha(-/-)) mic e to understand the role of IL-15R alpha in immune development and function . IL-15R alpha(-/-) mice are markedly lymphopenic despite grossly normal T and B lymphocyte development. This lymphopenia is due to decreased prolifer ation and decreased homing of IL-15R alpha(-/-) lymphocytes to peripheral l ymph nodes. These mice are also deficient in natural killer cells, natural killer T cells, CD8(+) T lymphocytes, and TCR gamma delta intraepithelial l ymphocytes. In addition, memory phenotype CD8(+) T cells are selectively re duced in number. Thus, IL-15R alpha has pleiotropic roles in immune develop ment and function, including the positive maintenance of lymphocyte homeost asis.