Enhanced survival and potent expansion of the natural killer cell population of HIV-infected individuals by exogenous interleukin-15

The CD56+CD16+ natural killer (NK) cell population plays a crucial role in eliminating virus-infected cells and is diminished in HIV-infected individuals. This study examined the effects of exogenous interleukin (IL)-15 on proliferation and survival of CD56+ and CD16+ cells of HIV-infected individuals. When used at equivalent concentrations in vitro, IL-15 was more potent than IL-2 as a growth factor for CD56+ cells, as well as for CD16+ cells and also CD4+ and CD8+ T cells. Analysis of cell survival in etoposide-treated cultures indicated that IL-15 was also more potent than IL-2 as a survival factor for CD56+ cells by virtue of its greater ability to up-regulate bcl-2 expression. Although IL-15-induced proliferation of CD56+ cells was accompanied by increased apoptosis, IL-15 was more effective than IL-2 in increasing the representation of viable CD56+ cells in the peripheral blood mononuclear cell population, but less effective in increasing T cell representation. The immunotherapeutic potential of IL-15 appears superior to IL-2 in regard to expanding NK cell populations in HIV-infected individuals, but needs to be weighed against poorer increases in T cell populations.