CD1d-reactive T-cell activation leads to amelioration of disease caused bydiabetogenic encephalomyocarditis virus

A subset of CD161 (NK1) T cells express an invariant V alpha 14J alpha 281 TCR-alpha chain (V alpha (invt) T cells) and produce Th2 and Th1 cytokines rapidly in response to CD1d, but their physiological function(s) remain unc lear. We have found that CD1d-reactive T cells mediate to resistance agains t the acute, cytopathic virus diabetogenic encephalomyocarditis virus (EMCV -D) in relatively Th1-biased, C57BL/6-based backgrounds. We show now that t hese results generalize to Th2-biased, hypersensitive BALB/c mice. CD1d-KO BALB/c mice were more susceptible to EMCV-D, Furthermore, ol-galactosylcera mide (alpha -GalCer), a CD1d-presented lipid antigen that specifically acti vates V-invt T cells, protected wild-type (WT) mice against EMCV-D-induced encephalitis, myocarditis, and diabetes. In contrast, neither CD1d-KO nor J alpha 281-KO mice were protected by alpha -GalCer, Finally, disease in J a lpha 281-KO mice was comparable to WT, indicating for the first time equiva lent roles for CDd-reactive V alpha (invt) and noninvariant T cells in resi stance to acute viral infection. A model for how CD1d-reactive T cells can initiate immune responses, which synthesizes current results, is presented.