IL-15 Enhances the Response of Human γδ T Cells to Nonpetide Microbial Antigens

Abstract

Human γδ T cells have the ability to rapidly expand and produce IFN-γ in response to nonpeptide Ags of microbial pathogens, in particular a class of compounds known as the prenyl phosphates. We investigated the ability of IL-15, a T cell growth factor, to modulate prenyl phosphate-induced γδ T cell proliferation and cytokine production. IL-15 significantly enhanced the expansion of γδ T cells in the peripheral blood after stimulation in vitro with isopentenyl pyrophosphate. Moreover, using γδ T cell clones, we determined that IL-15-induced T cell proliferation was dependent on the IL-2Rβ chain but not the IL-2Rα chain. We therefore studied the IL-15Rα chain expression in human γδ T cells in the presence or absence of nonpeptide Ags. We found IL-15Rα mRNA expression in IL-15-stimulated and Ag-stimulated human γδ T cells but not in resting γδ T cells. Although IL-15 itself had little effect on the production of IFN-γ, IL-15 plus IL-12 acted synergistically to augment IFN-γ production by γδ T cells. Moreover, we showed that this increase in IFN-γ could be explained by the dual activation of STAT1 and STAT4 by IL-15 and IL-12, respectively. Taken together, these results suggest that IL-15 may contribute to activation of human γδ T cells in the immune response to microbial pathogens.