IL-15 enhances survival and function of HIV-specific CD8+ T cells.

HIV-specific CD8(+) T cells are prone to undergo apoptosis, and this may affect their ability to control HIV infection. Because CD8-mediated immune responses play a key role in controlling HIV infection, enhancing the survival and effector function of HIV-specific CD8(+) T cells may augment their ability to control HIV virus. We show here that interleukin 15 (IL-15) potently inhibits spontaneous and CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells. IL-15 inhibits apoptosis in both CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-) effector memory subpopulations of these cells. Furthermore, IL-15 greatly enhances the survival of HIV-specific CD8(+) T cells in long-term cultures. Finally, IL-15 directly enhances activation, interferon gamma (IFNgamma) production, and direct ex vivo cytotoxicity of HIV-specific CD8(+) T cells. Thus, IL-15 potently enhances the survival and effector function of HIV-specific CD8(+) T cells and, therefore, may prove useful in augmenting the antiviral function of these cells.