| Initiation of myocarditis is mainly associated with a variety of infections, especially viral infections. The disease may then be perpetuated by immune- and autoimmune-mediated injury. Cardiac myosin is the major autoantigen in autoimmune myocarditis. Cellular immunity has been recognized as the principal mechanism for autoimmune myocarditis, whereas there is no conclusive evidence that humoral immunity can directly cause myocardial injury. Lewis rats are widely used as an animal model for experimental autoimmune myocarditis (EAM). In the Lewis rat EAM model, we investigated the cellular and humoral pathogenic mechanisms of autoimmune myocarditis. Our study suggested that a cryptic epitope such as S2-16 of cardiac myosin, although not recognized by native antigen sensitized T cells, may play an important role in the initiation or perpetuation of autoimmune disease. Our study also demonstrated that immune tolerance to cardiac myosin is a dynamic process which is controlled by ADCs such as DCs and their cytokines. In EAM, our study together with others showed that cardiac autoantibodies are unlikely to have direct histopathological effects leading to cardiac injury. However, our study suggested that cardiac autoantibodies may compromise myocardial function by acting as agonists to the cell membrane receptors such as beta-AR. The cross-reaction of autoantibodies with cardiac myosin and beta-AR was demonstrated and may define the pathophysiological relevance of cardiac autoantibodies. Our studies investigated both cellular and humoral immunity in Lewis rat EAM, and emphasized both initiation and regulation aspects of the immune response in an animal model of myocarditis. |
