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T Cells to Nonpetide Microbial Antigens1
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Division of Dermatology and
Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90095;
Molecular Biology Institute and Departments of
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Medicine and
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Biological Chemistry and
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Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095; and
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Division of Rheumatology and Immunology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
Human 
T cells have the ability to rapidly expand and produce
IFN- 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 T cell proliferation and cytokine
production. IL-15 significantly enhanced the expansion of T
cells in the peripheral blood after stimulation in vitro with
isopentenyl pyrophosphate. Moreover, using T cell clones, we
determined that IL-15-induced T cell proliferation was dependent on the
IL-2Rß chain but not the IL-2R
chain. We therefore studied the
IL-15R chain expression in human T cells in the presence or
absence of nonpeptide Ags. We found IL-15R mRNA expression in
IL-15-stimulated and Ag-stimulated human T cells but not in
resting T cells. Although IL-15 itself had little effect on the
production of IFN-, IL-15 plus IL-12 acted synergistically to
augment IFN- production by T cells. Moreover, we showed that
this increase in IFN- 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
T cells in the immune response to microbial pathogens.
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