Monocytes prime autoreactive T cells after myocardial infarction

摘要

Following myocardial infarction (MI), interruption of blood flow leads to rapid ischemic death of cardiomyocytes. Release of damage-associated molecular patterns and debris by necrotic cardiomyocytes stimulate inflammation and recruitment of phagocytes, including Ly6Chl monocytes and dendritic cells. During phagocytic clearance of necrotic debris, cardiac self-antigen can be processed and then presented in the heart-draining lymph nodes to a-MHC-specific CD4+ T cells (22), which escape thymic negative selection (16), triggering an autoimmune response directed against the heart. In the general population, this presents as transient-cellular and humoral responses directed against cardiac myosin (17, 18). However, in patients with type 1 diabetes, this response can develop into a persistent autoimmune myocarditis (9), which may contribute to the worsened outcomes in patients with type 1 diabetes after MI (21). In both type 1 diabetes and postinfarction autoimmu-nity, autoreactive CD4+ T cells display Thl polarization and are characterized by proinflammatory interferon (EFN)-'Y production (1, 9). While conventional dendritic cells have been shown to prime a-MHC-specific CD4+ T-cell responses (22), in some instances they are not required for postinfarction autoimmunity, necessitating a better understanding of the role of alternative innate immune cells in cardiac self-antigen trafficking and antigen presentation after MI.