CELLULAR AND MOLECULAR MECHANISMS OF MURINE AUTOIMMUNE MYOCARDITIS

Dilated cardiomyopathy is a prevalent cause of progressive heart disea se and sudden death, and most patients with cardiomyopathy have a hist ory of viral myocarditis. Coxsackie B3 (CB3) picornaviruses can be det ected in as many as 50% of these patients and CB3 infections have been epidemiologically linked to chronic heart disease. Several clinical a nd experimental studies suggest that chronic stages of disease are med iated by an autoimmune response against heart muscle myosin. Human hea rt disease can be mimicked in mice using cardiac myosin as autoantigen . Murine cardiac myosin-induced myocarditis is an organ-specific autoi mmune disease and mediated by CD4(+) T cells that recognize a myosin-s pecifre peptide in association with MHC class II molecules. Here, the recent discovery of autoimmune epitopes derived from the alpha isoform of cardiac myosin, the functional roles of surface receptor and signa l transduction molecules, and the molecular mechanisms of target organ susceptibility will be discussed.