T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.

BACKGROUND: In viral myocarditis, we previously reported that natural killer cells infiltrate the heart first, then activated T cells infiltrate second and play an important role in the pathogenesis of the myocardial damage. METHODS AND
RESULTS: To elucidate the nature of T-cell infiltration, using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the expression of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart by polymerase chain reaction (PCR). The PCR-amplified products were confirmed by Southern blot hybridization with a C beta cDNA probe. In contrast to spleen lymphocytes, the repertoire of V beta gene transcripts in the heart was restricted. The infiltrating cells expressing V beta 10 were found in six of eight hearts of mice with acute myocarditis. The infiltrating cells expressing V beta 8 and V beta 13 were found in four of eight hearts with myocarditis, respectively. Immunoperoxidase staining of serial sections of the heart of myocarditis for TCR alpha beta chains and TCR V beta 10 confirmed that the dominant population of infiltrating T cells expressed V beta 10 gene products.
CONCLUSIONS: The restricted usage of TCR genes by infiltrating T-cells may indicate that a specific antigen in heart with myocarditis is targeted. Our findings raise the possibility of immunotherapy with monoclonal antibodies specific for TCR V beta elements to prevent T-cell-mediated myocardial damage in viral myocarditis.