Restricted usage of T-cell receptor V alpha genes in infiltrating cells in murine hearts with acute myocarditis caused by coxsackie virus B3.

Abstract

In murine myocarditis, it has been shown that natural killer cells first infiltrate the heart, followed by activated T-cells, which play an important role in the pathogenesis of the myocardial damage. In the same model of acute myocarditis, the repertoire of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart has also been shown to be restricted. To study the nature of T-cell infiltration in more detail, the expression of TCR V alpha genes in infiltrating cells in the heart has been analysed by the polymerase chain reaction (PCR), confirmed by Southern blot hybridization with a C alpha cDNA probe. In contrast to spleen lymphocytes, the repertoire of V alpha gene transcripts in the heart was restricted. Infiltrating cells expressing V alpha 10 were found in five of eight hearts of mice with acute myocarditis and infiltrating cells expressing V alpha 7 and V alpha 3 were found in two of eight and one of eight hearts, respectively. Restricted TCR V alpha as well as V beta repertoires indicate that a specific antigen, in the heart was targeted, presented at the groove of major histocompatibility complex molecules. These findings raise the possibility of specific immunotherapy with synthetic TCR V alpha or V beta peptides to prevent T-cell-mediated myocardial damage in patients with viral myocarditis.