Interleukin-15 receptor alpha (IL-15Rα) is a pleiotropically expressed molecule that chaperones and trans-presents IL-15 to NK and T cells. To investigate whether IL-15Rα presented by different cells perform distinct physiological functions, we have generated four lines of mice lacking IL-15Rα in various cell types. We find that IL-15Rα expression on macrophages but not dendritic cells (DCs) supports the early transition of antigen specific effector CD8+ T cells to memory cells. After memory CD8+ T cell differentiation, IL-15Rα expression on DCs selectively supports central memory CD8+ T cells, whereas IL-15Rα expression on macrophages supports both central and effector memory CD8+ T cells. By contrast, mice lacking IL-15Rα on macrophages, DCs, or both, exhibit equivalent defects in NK cell homeostasis and activation. These studies define unique roles for macrophage expression of IL-15Rα and show that NK cells rely upon distinct IL-15Rα dependent IL-15 signals than memory CD8+ T cells. Moreover, they demonstrate the diversity, specification, and geographic restriction of cytokine signals.
