Prevention of autoimmune myocarditis through the induction of antigen-specific peripheral immune tolerance

Background-Autoimmunity to cardiac antigens, in particular cardiac myosin, has been observed in humans with myocarditis and in animals with experiment al inflammatory heart disease. Current treatments for myocarditis are in ma ny cases immunosuppressive and might lead to increased cardiac damage by re ducing host defenses against infectious agents. Therefore, we sought to dev elop an antigen-specific approach to inhibit autoimmunity in mice with myos in-induced experimental autoimmune myocarditis. Methods and Results-Syngeneic splenocytes, coupled with cardiac myosin by u se of ethylene carbodiimide, were administered intravenously before disease induction, and the effects of this peripheral tolerization on myosin-induc ed myocarditis were assessed. This antigen-specific immunotherapy significa ntly reduced both the incidence and severity of myocarditis, with the preve ntion of myocyte necrosis, mononuclear cell infiltration, and fibrosis. Myo sin-specific delayed-type hypersensitivity and antibody production were sig nificantly reduced, demonstrating that peripheral tolerance affected both T - and B-cell responsiveness to the autoantigen. Conclusions-These results suggest that the induction of antigen-specific pe ripheral immune tolerance may be an effective approach for the treatment of myocarditides with autoimmune involvement.