Myosin Autoreactive T Cells And Autoimmune Myocarditis. Lessons from the Disease Caused by Cardiac Myosin Peptide CM2

Abstract

We have proposed a unique animal model of experimental autoimmune myocarditis (EAM). This rat myocarditis is systematically provoked by immunization with cardiac myosin, and evolves toward dilated cardiomyopathy through repetitive immunizations. In this process, myosin epitopes, dendritic cells and myosin autoreactive T cells are the three major elements initiating and promoting this disease. Despite many attempts, we have failed, thus far, to identify myosin autoreactive and myocarditogenic T cells in vitro. However, recently, T cell lines specifically reactive to the cardiac myosin peptide, CM 2 (AA: 1539-1555), and showing myocarditogenecity have been identified. Line characterization of harvested T cells from EAM rats rendered ill by whole cardiac myosin was repetitively and systematically tested. Thus, T cell lines autoreactive to CM 2 and inducing transfer myocarditis were isolated out of many candidates. Acute myocarditis transferred by means of these T cell lines became more severe, and disease transfer with these cell lines caused chronic myocarditis in syngenic Lewis rat. Importantly, the myosin autoreactive and myocarditogenic T cells were also able to transfer the myocarditis into SCID mice beyond the MHC restriction.