IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells

Abstract

IL-15 stimulates the proliferation of memory phenotype CD44 high CD8 + T cells and is thought to play a key role in regulating the turnover of these cells in vivo. We have investigated whether IL-15 also has the capacity to affect the life span of naive phenotype (CD44 low ) CD8 + T cells. We report that IL-15 promotes the survival of both CD44 low and CD44 high CD8 + T cells, doing so at much lower concentrations than required to induce proliferation of CD44 high cells. Rescue from apoptosis was associated with the up-regulation of Bcl-2 in both cell types, whereas elevated expression of Bcl-x L was observed among CD44 high but not CD44 low CD8 + cells. An investigation into the role of IL-15R subunits in mediating the effects of IL-15 revealed distinct contributions of the α- and β- and γ-chains. Most strikingly, IL-15Rα was not essential for either induction of proliferation or promotion of survival by IL-15, but did greatly enhance the sensitivity of cells to low concentrations of IL-15. By contrast, the β- and γ-chains of the IL-15R were absolutely required for the proliferative and pro-survival effects of IL-15, although it was not necessary for CD44 high CD8 + cells to express higher levels of IL-15Rβ than CD44 low cells to proliferate in response to IL-15. These results show that IL-15 has multiple effects on CD8 T cells and possesses the potential to regulate the life span of naive as well as memory CD8 + T cells.