Vγ1+γδT, early cardiac infiltrated innate population dominantly producing IL-4, protect mice against CVB3 myocarditis by modulating IFNγ+ T response

Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. V?1+??T cells, one of early cardiac infiltrated innate population, were reported to pro- tect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of V?1+??T and mechanism of protection against VMC, flow cytometry was conducted on car- diac V?1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of V?1??T. We found that V?1+??T cells infiltration peaked in the heart at day3 post CVB3 infection and consti- tuted a minor source of IFN-? but major producers for early IL-4. V?1??T cells were activated earlier holding a higher IL-4-producing efficiency than CD4+Th cells in the heart. Depletion of V?1+??T resulted in a significantly exacerbated cardiac infiltration, increased T, macrophage and neutrophil population in heart homogenates and worse cardiomyopathy; which was accompanied by a significant expansion of peripheral IFN?+CD4+ and CD8 + T cells. Neutralization of IL-4 in mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated protective mechanism of V?1. Our findings identify a unique property of V?1+??T cells as one dominant early producers of IL-4 upon CVB3 acute infection which is a key mediator to protect mice against acute myocarditis by modulating IFN?-secreting T response.