Regulating viral myocarditis: allografted regulatory T cells decrease immune infiltration and viral load.

Coxsackievirus was first discovered as a filterable agent associated with a paralytic syndrome, so named for its identification in Coxsackie, New York (coxsackievirus type A).1 Coxsackievirus type B (CVB) was isolated the following year from patients with aseptic meningitis,2 and by the mid-1950s, an association with acute myocarditis in humans was becoming clear.3–6 Many other viruses have since been shown to cause myocarditis and its long-term sequelae, arrhythmias, dilated cardiomyopathy, and heart failure. By example, adenovirus, herpesviruses, and influenza can cause myocarditis in humans and models of heart failure. Because immune cell infiltration is an easily seen feature of myocarditis, it is perhaps not surprising that the inflammatory response would be posited as a major cause of tissue injury during viral myocarditis. However, the virus itself has lytic and destructive potential, and a range of data indicate both viral and immune contributions to cardiomyocyte and interstitial damage during myocarditis. The question is often posed: Is damage primarily virus-mediated or more so the product of an overzealous immune response and autoimmunity? Perhaps the greatest error in the discussion has been approaching these 2 facets of the disease process in a mutually exclusive manner. Shi et al7 now show in this issue of Circulation that virus replication and the immune response are exquisitely intertwined in myocarditis pathogenesis.