Abstract
For more than a half century, autoimmunity has been linked to a diverse array of heart diseases, including rheumatic carditis, myocarditis, Chagas' cardiomyopathy, post-myocardial infarction (Dressler's) syndrome, and idiopathic dilated cardiomyopathy. Why the heart is targeted by autoimmunity in these seemingly unrelated conditions has remained enigmatic. Here, we discuss our recent studies indicating that this susceptibility is mediated by impaired negative selection of autoreactive α-myosin heavy-chain-specific CD4(+) T cells in the thymus of both mice and humans. We describe how this process may place the heart at increased risk for autoimmune attack following ischemic or infectious injury, providing a rationale for the development of antigen-specific tolerogenic therapies.