Coxsackievirus B3 infections of C57BL/6 mice, which express the MHC class II IA but not IE Ag, results in virus replication in the heart but minimal myocarditis. In contrast, Bl.Tg.Eα mice, which are C57BL/6 mice transgenically induced to express IE Ag, develop significant myocarditis upon Coxsackievirus B3 infection. Despite this difference in inflammatory damage, cardiac virus titers are similar between C57BL/6 and Bl.Tg.Eα mice. Removing γδ T cells from either strain by genetic manipulation (γδ knockout(ko)) changes the disease phenotype. C57BL/6 γδ ko mice show increased myocarditis. In contrast, Bl.Tg.Eα γδ ko mice show decreased cardiac inflammation. Flow cytometry revealed a difference in the γδ cell subsets in the two strains, with Vγ1 dominating in C57BL/6 mice, and Vγ4 predominating Bl.Tg.Eα mice. This suggests that these two Vγ-defined subsets might have different functions. To test this possibility, we used mAb injection to deplete each subset. Mice depleted of Vγ1 cells showed enhanced myocarditis, whereas those depleted of Vγ4 cells suppressed myocarditis. Adoptively transfusing enriched Vγ4+ cells to the C57BL/6 and Bl.Tg.Eα γδ ko strains confirmed that the Vγ4 subset promoted myocarditis. Th subset analysis suggests that Vγ1+ cells biased the CD4+ T cells to a dominant Th2 cell response, whereas Vγ4+ cells biased CD4+ T cells toward a dominant Th1 cell response.

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