Two Sides to Every Proinflammatory Coin

Myocarditis is a major cause of heart failure in young adults that is typically precipitated by cardiac infection with organisms such as Coxsackie B virus or the parasite Trypanosoma Cruzi 1 . Myocarditis has a variety of clinical presentations but is often characterized by severe ventricular dysfunction and risk of fatal arrhythmia. Tissue injury during myocarditis is caused by direct infection of cardiomyoctes and immune-mediated responses to microbial antigens; in addition, autoimmune T cell and antibody responses to myocardial antigens can develop and persist even after the inciting infection has been cleared. The autoimmune component of myocarditis indicates a failure of self-tolerance mechanisms, and may be driven by molecular mimicry between microbial and myocardial self-antigens. Although there has been an emphasis on the role of autoantibodies in autoimmune myocarditis, such as those targeting the β1 adrenergic receptor or the αmyosin heavy chain αMHC), this may reflect the relative ease of their experimental detection as compared to assays of T cell activation by specific self-antigens. Nonetheless, the relevance of T cells is supported by the fact that lymphocytic infiltrates including CD4 + helper T cells can be demonstrated in endocardial biopsy or autopsy sections taken from patients with myocarditis, and by the fact that many of the cardiac auto-antibodies in human myocarditis have undergone IgG class switching, which reflects T helper dependent B cell responses.