| CD8+ T cells are a vital component of the cellular immune response and can confer protective immunity to viruses and intracellular bacteria. Recent studies in a number of model systems have found that the cytokine interleukin (IL)-15 and its unique receptor, IL-15Rα, play critical roles in supporting the long term survival and proliferation of memory CD8+ T cells. Using an adoptive transfer model of CD8+ T cell memory, we have found that although IL-15Rα expression on memory CD8+ T cells is dispensable, IL-15Rα expression by a cell type other than the CD8+ T cell is required for the long-term maintenance of memory CD8+ T cells. The non-cell autonomous requirement for IL-15Rα in order to support memory CD8+ T cells may be related to the ability of IL-15Rα to bind and present IL-15 in trans. Consistent with this hypothesis, we have found that in vitro, IL-15Rα/Fc can bind IL-15 and support the survival and proliferation of memory CD8+ T cells. Moreover, bone marrow chimera experiments suggest that while IL-15Rα expression by either radiation sensitive or radiation resistant cells is sufficient to allow the development of long lived memory CD8+ T cells, optimal memory CD8+ T cell survival and proliferation requires the coordinate expression of both IL-15 and IL-15Rα by a radiation sensitive, RAG-I independent cell type. Finally, IL-2/15Rβ expression is not required on supporting cells, further indicating that trans presentation of IL-15 by IL-15Rα is the dominant mechanism for supporting memory CD8+ T cell survival in vivo. Taken together, these findings suggest that regulation of IL-15Rα expression by innate immune cells may represent an important mechanism for controlling memory CD8+ T cell homeostasis. |
