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

A subset of CD161 (NK1) T cells express an invariant Vα14Jα281TCR‐α chain (Vαinvt T cells) and produce Th2 and Th1cytokines rapidly in response to CD1d, but their physiologicalfunction(s) remain unclear. We have found that CD1d‐reactive T cellsmediate to resistance against the acute, cytopathic virus diabetogenicencephalomyocarditis virus (EMCV‐D) in relatively Th1‐biased,C57BL/6‐based backgrounds. We show now that these results generalize toTh2‐biased, hypersensitive BALB/c mice. CD1d‐KO BALB/c mice were moresusceptible to EMCV‐D. Furthermore, α‐galactosylceramide(α‐GalCer), a CD1d‐presented lipid antigen that specificallyactivates Vαinvt T cells, protected wild‐type (WT) miceagainst EMCV‐D‐induced encephalitis, myocarditis, and diabetes. Incontrast, neither CD1d‐KO nor Jα281‐KO mice were protected byα‐GalCer. Finally, disease in Jα281‐KO mice was comparable to WT, indicating for the first time equivalent roles for CD1d‐reactiveVαinvt and noninvariant T cells in resistance to acuteviral infection. A model for how CD1d‐reactive T cells can initiateimmune responses, which synthesizes current results, ispresented.