T Cells Expressing the Vγ1 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 Vγ4 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 Vγ1+ cells. No significant differences in CD11b+ (monocyte) cells were observed between the sexes. Infected males showed a predominant CD4+Th1 (IFNγ+) response, whereas females showed a predominant CD4+Th2 response. The importance of IFNγ for myocarditis susceptibility and IL-4 for protection was confirmed using IFN-γ−/− and IL-4−/− mice. Antibody depletion of Vγ1+ cells augmented myocarditis susceptibility, whereas antibody depletion of Vγ4+ cells was protective. Cardiac virus titers inversely correlated with virus neutralizing antibodies and showed that Vγ1+ cells are important for virus neutralizing antibody response. IFNγ affected the Vγ4+ cell response in the heart, as IFNγ−/− mice had few Vγ4+ cells; but exogenous administration of recombinant IFNγ to IFNγ−/− mice restored myocarditis susceptibility, Th1 bias, and Vγ4+ cell infiltration of the myocardium. These results demonstrate that two γδ+ T cell populations, Vγ1+ and Vγ4+, have different functions during myocarditis, in that Vγ1+ cells promote humoral immunity and protection whereas Vγ4+ cells are pathogenic.