Coordinate Expression and Trans Presentation of Interleukin (IL)-15Rα and IL-15 Supports Natural Killer Cell and Memory CD8+ T Cell Homeostasis

Abstract

The high affinity interleukin (IL)-15 receptor, IL-15Rα, is essential for supporting lymphoid homeostasis. To assess whether IL-15Rα's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Rα– and IL-2/15Rβ–deficient mice. We find that IL-15Rα–competent, IL-2/15Rβ–deficient cells are able to support IL-15Rα–deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Rα–mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Rα functions in vivo. Surprisingly, using IL-15– and IL-15Rα–deficient mixed chimera, we also find that IL-15 and IL-15Rα must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Rα is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Rα defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.