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14+CD4+NKT Cells: Stimulation of IL-12 Production by Antigen-Presenting Cells in the Innate Immune System1
*
Biomedical Research Center, Osaka University Medical School, Osaka, Japan;
Core Research for Evolutional Science and Technology Project, Japan Science and Technology Corporation and Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
Pharmaceutical Research Laboratory, Kirin Brewery, Gunma, Japan
The balance between Th1 and Th2 development is determined by IL-4
and IL-12. While the role for CD4+ NK1.1+ T
(NKT) cells in influencing this balance has been recognized based on
their capacity to produce IL-4, it is unknown how IL-12 is produced in
the innate immune system in which they participate. This study
demonstrates that Ag-activated CD4+ NKT cells express CD40
ligand (CD40L) (CD154), which engages CD40 on APC and stimulates them
to produce IL-12. Culture of B cell-depleted spleen cells from C57BL/6
mice with 
-galactosylceramide (-GalCer) capable of selectively
stimulating V14/J281+ NKT cells resulted in the
production of IL-12 together with IFN-
and IL-4. -GalCer-induced
IL-12 production occurred in I-Abß-deficient mice, but
not in ß2-microglobulin-deficient and V14/J281
TCR-deficient mice, and was inhibited by anti-CD40L mAb. Of
CD4+ and CD4- NKT cells, the capacity to
express CD40L/CD154 and trigger IL-12 production following -GalCer
stimulation was exhibited preferentially by the CD4+ NKT
subset. IL-12 production was also observed in -GalCer-treated mice.
Production of IL-12 preceded IFN- production, and IL-12 was required
for IFN-, but not IL-4, production. A stimulatory/inhibitory
relationship existed between IL-12 and IL-4 production. These results
illustrate a novel function of CD4+ NKT cells that could be
involved in the regulation of Th1 vs Th2
development.
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