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

Coxsackievirus B3 infection causes severe cardiac inflammation in male but not female mice. CD3+ T cells and T cells expressing the V gamma 4 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 V gamma 1+ cells. No significant differences in CD11b+ (monocyte) cells were observed between the sexes. Infected males showed a predominant CD4+Th1 (IFN gamma+) response, whereas females showed a predominant CD4+Th2 response. The importance of IFN gamma for myocarditis susceptibility and IL-4 for protection was confirmed using IFN-gamma-/- and IL-4-/- mice. Antibody depletion of V gamma 1+ cells augmented myocarditis susceptibility, whereas antibody depletion of V gamma 4+ cells was protective. Cardiac virus titers inversely correlated with virus neutralizing antibodies and showed that V gamma 1+ cells are important for virus neutralizing antibody response. IFN gamma affected the V gamma 4+ cell response in the heart, as IFN gamma-/- mice had few V gamma 4+ cells; but exogenous administration of recombinant IFN gamma to IFN gamma-/- mice restored myocarditis susceptibility, Th1 bias, and V gamma 4+ cell infiltration of the myocardium. These results demonstrate that two gamma delta+ T cell populations, V gamma 1+ and V gamma 4+, have different functions during myocarditis, in that V gamma 1+ cells promote Immoral immunity and protection whereas V gamma 4+ cells are pathogenic.