Immune tolerance to cardiac myosin induced by anti-CD4 monoclonal antibody in autoimmune myocarditis rats

Autoimmune myocarditis is a T-cell-mediated autoimmune disease. CD4-positive T cells are believed to be the most important for the initiation and mediation of the disease. This study was aimed at evaluating whether anti-CD4 monoclonal antibody could induce immune tolerance to porcine cardiac myosin and whether the immune tolerance could protect rats with autoimmune myocarditis from myocardial injury. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis. Immune tolerance was induced by injections of anti-CD4 monoclonal antibody on days -2, -1, 0, and 1. Results showed that cardiac function of antibody-treated rats was significantly increased compared with untreated rats 18 days postimmunization examined by transthoracic echocardiography. Typical cardiac histopathological changes were observed obviously in untreated group but not in antibody-treated group. Lymphocytes obtained from antibody-treated group had no proliferative response to porcine cardiac myosin examined by lymphocyte proliferation assay. Serological examination showed that rats immunized with cardiac myosin could produce high levels of anti-cardiac myosin antibody. The administration of anti-CD4 monoclonal antibody significantly prevented the increase of them. Serum levels of Th1 cytokines were significantly down-regulated by antibody administration, while the production of Th2 cytokines were up-regulated or unaffected evaluated by enzyme-linked immunosorbent assay. It concluded that immune tolerance to porcine cardiac myosin could be induced by anti-CD4 monoclonal antibody in vivo, and cardiac dysfunction and myocardial injury could be prevented by induction of immune tolerance.