Myocarditis: a defect in central immune tolerance?

Abstract

Myocarditis, or inflammation of the heart, is a potentially devastating disease that can result from both viral infection and autoimmune attack of self antigens in the heart. In the current issue of the JCI, Lv and colleagues use a genetically susceptible mouse model to show that myocarditis is a T cell-mediated autoimmune disease that occurs due to insufficient thymic negative selection of α-myosin-reactive T cells.

Figure 1. Permissive negative selection leads to myocarditis in DQ8⁺NOD mice.

In DQ8⁺NOD mice (A), α-myosin–reactive T cells escape the thymus, presumably due to the absence of negatively selecting α-myosin antigen within the thymus. These T cells are then able to recognize their target antigen within the heart and heart-draining lymph nodes, causing inflammation and myocarditis. When α-myosin is transgenically introduced into thymic epithelial cells (TEC) of this same mouse strain (B; TOM⁺TA⁺DQ8⁺NOD mice), negative selection likely induces deletion of developing α-myosin–reactive T cells, preventing their maturation, egress to the periphery, and infiltration of the heart.