Activation, survival and apoptosis of CD45RO(+) and CD45RO(-) T cells of human immunodeficiency virus-infected individuals: effects of interleukin-15and comparison with interleukin-2

HIV infection is associated with increased representation of T cells bearin g an activated, memory (CD45RO(+)) phenotype. Although administration of an tiretroviral agents and interleukin-2 (IL-2) augment depleted CD4(+) T-cell numbers, such therapies have been preferentially beneficial for CD45RO(+) T cells. Interleukin-15 (IL-15) exhibits many biological activities in comm on with IL-2, including promoting T-cell survival and proliferation. The pr esent study found that these two cytokines differed in their ability to ind uce proliferation, enhance survival, and control apoptosis of CD45RO(+) and CD45RO(-) T-cell populations of human immunodeficiency- (HIV) infected ind ividuals. When used at equivalent concentrations in vitro, IL-15 was more p otent than IL-2 in activating and stimulating proliferation of CD4(+)CD45RO (+), CD8(+)CD45RO(+) and CD8(+)CD45RO(-) cells, but failed to be more effec tive than IL-2 in reducing apoptosis. Poor activation of CD4(+)CD45RO(-) ce lls by IL-15 and to IL-2 appeared to be attributable to low expression of t he beta receptor chain utilized by both cytokines. However, IL-15 was more effective than IL-2 in enhancing survival of the CD4(+)CD45RO(-) population , suggesting a greater protective effect of IL-15 for naive CD4(+) T cells, which are preferentially lost in HIV-infected individuals.