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

Abstract

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) Vβ genes in infiltrating cells in the heart by polymerase chain reaction (PCR). The PCR-amplified products were confirmed by Southern blot hybridization with a Cβ cDNA probe. In contrast to spleen lymphocytes, the repertoire of Vβ gene transcripts in the heart was restricted. The infiltrating cells expressing Vβ10 were found in six of eight hearts of mice with acute myocarditis. The infiltrating cells expressing Vβ8 and Vβ13 were found in four of eight hearts with myocarditis, respectively. Immunoperoxidase staining of serial sections of the heart of myocarditis for TCR αβ chains and TCR Vβ10 confirmed that the dominant population of infiltrating T cells expressed Vβ10 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 Vβ elements to prevent T-cell-mediated myocardial damage in viral myocarditis.