Coxsackieviruses are a cause of clinical myocarditis. Both virus replication and host defense mechanisms, including virus-induced autoimmunity, mediate heart injury and cardiac dysfunction. Vgamma4+ cells kill infected cardiocytes and virus-specific CD4+ Th2 cells through Fas-dependent apoptosis and CD1d. The CD4+ Th1 response is necessary for activation of the autoimmune CD8+ T cells, which kill uninfected cardiocytes through perforin-dependent mechanisms.