* Cancer Biology Program, Hematology/Oncology Division, Beth Israel-Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts;
Harvard School of Public Health, Boston, Massachusetts;
Microbiology/Immunology, Wright State University, Dayton, Ohio;
|| Core Research in Evolution, Science, and Technology (CREST), Chiba University, Chiba, Japan; and
Kirin Brewery Corporation, Ltd., Japan
Correspondence: Dr. Mark A. Exley, Cancer Biology, HIM 1047, Hematology/Oncology, Beth Israel-Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: mexley{at}caregroup.harvard.edu
A subset of CD161 (NK1) T cells express an invariant V
14J281
TCR- chain (Vinvt T cells) and produce Th2 and Th1
cytokines rapidly in response to CD1d, but their physiological
function(s) remain unclear. We have found that CD1d-reactive T cells
mediate to resistance against the acute, cytopathic virus diabetogenic
encephalomyocarditis virus (EMCV-D) in relatively Th1-biased,
C57BL/6-based backgrounds. We show now that these results generalize to
Th2-biased, hypersensitive BALB/c mice. CD1d-KO BALB/c mice were more
susceptible to EMCV-D. Furthermore, -galactosylceramide
(-GalCer), a CD1d-presented lipid antigen that specifically
activates Vinvt T cells, protected wild-type (WT) mice
against EMCV-D-induced encephalitis, myocarditis, and diabetes. In
contrast, neither CD1d-KO nor J281-KO mice were protected by
-GalCer. Finally, disease in J281-KO mice was comparable to WT,
indicating for the first time equivalent roles for CD1d-reactive
Vinvt and noninvariant T cells in resistance to acute
viral infection. A model for how CD1d-reactive T cells can initiate
immune responses, which synthesizes current results, is
presented.
Key Words: diabetes • encephalitis • IL-12 • BALB/c mice • Vinvt • knockout mice
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