Susceptibility to Myocarditis Is Dependent on the Response of ab T Lymphocytes to Coxsackieviral Infection

Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4), CD8 (CD8), both coreceptors (CD4CD8), or the T-cell receptor b chain (TCRb) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8 mice but attenuated in CD4 mice, consistent with a pathogenic role for CD4 lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4 and CD8 T cells contribute to host susceptibility. The same benefit occurred in TCRb mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferon-g and decreased tumor necrosis factor-a expression are associated with attenuated myocardial damage in CD4CD8 mice. These results show that the presence of TCRab T cells enhances host susceptibility to myocarditis. The severity of myocardial damage and associated mortality are dependent on the predominant T-cell type available to respond to CVB3 infection. One mechanism by which CD4 and CD8 T-cell subsets influence the pathogenesis of myocarditis may involve specific cytokine expression patterns. (Circ Res. 1999;85:551-558.)