V gamma 1(+) T cells suppress and V gamma 4(+) T cells promote susceptibility to coxsackievirus B3-induced myocarditis in mice

Coxsackievirus B3 infections of C57BL/6 mice, which express the MHC class I I IA but not IE Ag, results in virus replication in the heart but minimal m yocarditis. In contrast, B1.Tg.E alpha mice, which are C57BL/6 mice transge nically induced to express IE Ag, develop significant myocarditis upon Coxs ackievirus B3 infection. Despite this difference in inflammatory damage, ca rdiac virus titers are similar between C57BL16 and B1.Tg.E alpha mice. Remo ving gamma delta T cells from either strain by genetic manipulation (gamma delta knockout(ko)) changes the disease phenotype, C57BL/6 gamma delta ko m ice show increased myocarditis, In contrast, B1.Tg.E alpha gamma delta ko m ice show decreased cardiac inflammation. Flow cytometry revealed a differen ce in the gamma delta cell subsets in the two strains, with V gamma 1 domin ating in C57BL16 mice, and V gamma 4 predominating B1.Tg.E alpha mice. This suggests that these two V gamma-defined subsets might have different funct ions. To test this possibility, we used mAb injection to deplete each subse t. Mice depleted of V gamma 1 cells showed enhanced myocarditis, whereas th ose depleted of V gamma 4 cells suppressed myocarditis, Adoptively transfus ing enriched V gamma 4(+) cells to the C57BL/6 and B1.Tg.E alpha gamma delt a ko strains confirmed that the V gamma 4 subset promoted myocarditis, Th s ubset analysis suggests that V gamma 1(+) cells biased the CD4(+) T cells t o a dominant Th2 cell response, whereas V gamma 4(+) cells biased CD4(+) T cells toward a dominant Th1 cell response.