T Cells in Coxsackievirus-Induced Myocarditis

Abstract

Myocarditis is a complex disease in which distinct immunopathogenic mechanisms cause tissue injury. In some but not all cases, autoimmunity is a major pathogenic factor. Cross-reactivity between viral and myosin epitopes underlies both cellular and humoral autoimmunity in myocarditis. Thus, the genetics of the host as well as the virus determine disease pathogenicity. Innate immunity, as represented by γδ+ T cells, is important in determining disease susceptibility. The innate effectors rapidly localize in the infected myocardium and through release of IFNγ (Vγ4+ cells; BALB/c) or IL-4 (Vγ1+ cells; C57Bl/6), modulate the developing adaptive immune response to either a Th1 or Th2 response, respectively. The Vγ4+ cells in BALB/c mice recognize CD1d, a major histocompatibility complex class I-like antigen. The ligand for Vγ1+ cells is unknown. Only infected myocytes up-regulate CD1d. Signaling through both infection (double stranded RNA) and TNFα is required for CD1d up-regulation.