IL-15 ENHANCES THE RESPONSE OF HUMAN GAMMA-DELTA T-CELLS TO NONPEPTIDE MICROBIAL ANTIGENS

Human gamma delta T cells have the ability to rapidly expand and produ ce IFN-gamma in response to nonpeptide Ags of microbial pathogens, in particular a class of compounds known as the prenyl phosphates. We inv estigated the ability of IL-15, a T cell growth factor, to modulate pr enyl phosphate-induced gamma delta T cell proliferation and cytokine p roduction. IL-15 significantly enhanced the expansion of gamma delta T cells in the peripheral blood after stimulation in vitro with isopent enyl pyrophosphate. Moreover, using gamma delta T cell clones, we dete rmined that IL-15-induced T cell proliferation was dependent on the IL -2R beta chain but not the IL-2R alpha chain. We therefore studied the IL-15R alpha chain expression in human gamma delta T cells in the pre sence or absence of nonpeptide Ags. We found IL-15R alpha mRNA express ion in IL-15-stimulated and Ag-stimulated human gamma delta T cells bu t not in resting gamma delta T cells. Although IL-15 itself had little effect on the production of IFN-gamma, IL-15 plus IL-12 acted synergi stically to augment IFN-gamma production by gamma delta T cells. Moreo ver, we showed that this increase in IFN-gamma could be explained by t he dual activation of STAT1 and STAT4 by IL-15 and IL-12, respectively , Taken together, these results suggest that IL-15 may contribute to a ctivation of human gamma delta T cells in the immune response to micro bial pathogens.