T cells expressing the Vgamma1 T-cell receptor enhance virus-neutralizing antibody response during coxsackievirus B3 infection of BALB/c mice: differences in male and female mice

Abstract

Coxsackievirus B3 infection causes severe cardiac inflammation in male but not female mice. CD3+ T cells and T cells expressing the Vgamma4 T cell receptor (TCR) predominate in the cardiac inflammatory cell infiltrate in infected male BALB/c mice. Infected females have mostly CD19+ (B lymphocyte) and Vgamma1+ cells. No significant differences in CD11b+ (monocyte) cells were observed between the sexes. Infected males showed a predominant CD4+Th1 (IFNgamma+) response, whereas females showed a predominant CD4+Th2 response. The importance of IFNgamma for myocarditis susceptibility and IL-4 for protection was confirmed using IFN-gamma-/- and IL-4-/- mice. Antibody depletion of Vgamma1+ cells augmented myocarditis susceptibility, whereas antibody depletion of Vgamma4+ cells was protective. Cardiac virus titers inversely correlated with virus neutralizing antibodies and showed that Vgamma1+ cells are important for virus neutralizing antibody response. IFNgamma affected the Vgamma4+ cell response in the heart, as IFNgamma-/- mice had few Vgamma4+ cells; but exogenous administration of recombinant IFNgamma to IFNgamma-/- mice restored myocarditis susceptibility, Th1 bias, and Vgamma4+ cell infiltration of the myocardium. These results demonstrate that two gammadelta+ T cell populations, Vgamma1+ and Vgamma4+, have different functions during myocarditis, in that Vgamma1+ cells promote humoral immunity and protection whereas Vgamma4+ cells are pathogenic.