Decay-Accelerating Factor (CD55) Promotes CD1d Expression and V γ 4+ T-Cell Activation in Coxsackievirus B3-Induced Myocarditis

Abstract

BALB/c mice infected with the H3 variant of Coxsackievirus B3 (CVB3) develop severe myocarditis which is initiated by up-regulation of CD1d during infection and CD1d-dependent activation of T cells expressing the Vγ4 T cell receptor. Previous studies have shown that a mutant variant of the H3 virus which shows reduced binding avidity to one of the known CVB3 virus receptors, decay accelerating factor (DAF), fails to up-regulate CD1d or activate Vγ4+ cells. To determine if DAF has a role in CD1d expression during infection or Vγ4+ cell activation, BALB/c and BALB/c DAF–/– mice were infected with CVB3. Infected DAF–/– mice show modest increases in CD1d expression compared to infected wild-type BALB/c mice; and although total numbers of Vγ4+ cells in the spleen are the same as in BALB/c mice, few Vγ4+ IFNγ+ cells are detected in infected DAF–/– animals. Vγ4+ cell depletion protects infected BALB/c mice from myocarditis but does not protect infected DAF–/– animals, indicating that Vγ4+ cells are not important to disease in these animals. Anti-CD8 depletion of CD8+ T cells protects infected BALB/c mice but aggravates disease in infected DAF–/– animals, indicating that the immunopathogenicity of viral myocarditis differs in the absence of the DAF virus receptor.