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

Abstract

IL-15 stimulates the proliferation of memory phenotype CD44highCD8+ 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 (CD44low) CD8+ T cells. We report that IL-15 promotes the survival of both CD44low and CD44high CD8+ T cells, doing so at much lower concentrations than required to induce proliferation of CD44high cells. Rescue from apoptosis was associated with the up-regulation of Bcl-2 in both cell types, whereas elevated expression of Bcl-xL was observed among CD44high but not CD44low 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 CD44highCD8+ cells to express higher levels of IL-15Rβ than CD44low 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.