Chronic myocarditis induced by T cells reactive to a single cardiac myosinpeptide: Persistent inflammation, cardiac dilatation, myocardial scarring and continuous myocyte apoptosis

Recent recognition that an autoimmune myocarditis may precede, and result i n, dilated cardiomyopathy has focused attention on immune mechanisms of myo cardial injury. In this paper, we describe a model of chronic autoimmune my ocarditis in the Lewis rat. The production of myocarditis has been previous ly described by this group and in brief is accomplished by a single tail ve in infusion of activated T cells specific for a 17-amino acid peptide from rat cardiac myosin. In this report, animals were followed for approximately 6 months post-T-cell infusion. Hearts from animals which received cardiac myosin specific T cells all showed extensive fibrosis associated with ongoi ng inflammation. Apoptosis, identified by TdT-mediated dUTP nick end labell ing (TUNEL), was identified as a mode of myocyte death in hearts with acute and chronic myocarditis but not in age- and sex-matched controls, Immunohi stochemistry was used to characterize the immune infiltrate and adhesion mo lecules in hearts with chronic myocarditis and these findings were compared to hearts with acute myocarditis. We propose that this rat model of chroni c myocarditis mimics human disease, since inflammation results in ventricul ar dilatation and myocyte hypertrophy reminiscent of dilated cardiomyopathy . This model offers potential for further investigation of immune, function al and possible therapeutic aspects of autoimmune related cardiomyopathies. (C) 2000 Academic Press.