IL-15 enhances the response of human gamma delta T cells to nonpeptide [correction of nonpetide] microbial antigens.
Human gamma delta T cells have the ability to rapidly expand and produce IFN-gamma 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 gamma delta T cell proliferation and cytokine production. IL-15 significantly enhanced the expansion of gamma delta T cells in the peripheral blood after stimulation in vitro with isopentenyl pyrophosphate. Moreover, using gamma delta T cell clones, we determined 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 presence or absence of nonpeptide Ags. We found IL-15R alpha mRNA expression in IL-15-stimulated and Ag-stimulated human gamma delta T cells but 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 synergistically to augment IFN-gamma production by gamma delta T cells. Moreover, we showed that this increase in IFN-gamma 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 gamma delta T cells in the immune response to microbial pathogens.
García
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VE
Division of Dermatology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Jullien
D
D
Song
M
M
Uyemura
K
K
Shuai
K
K
Morita
C T
CT
Modlin
R L
RL
D000942:Antigens, Bacterial / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000276:immunology; D011756:Diphosphates / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology
D000942:Antigens, Bacterial; D016207:Cytokines; D011756:Diphosphates; D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta