Myocarditis: a defect in central immune tolerance?
Todd C. Metzger, Mark S. Anderson
Todd C. Metzger, Mark S. Anderson
Published March 23, 2011
Citation Information: J Clin Invest. 2011;121(4):1251-1253. https://doi.org/10.1172/JCI57211.
View: Text | PDF
Commentary

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.

Authors

Todd C. Metzger, Mark S. Anderson

×

Figure 1

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

Options: View larger image (or click on image) Download as PowerPoint
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.