T-bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-γ by γδ T cells

gammadelta T cells predominantly produce IFN-gamma upon activation. To determine the basis for default production of IFN-gamma by gammadelta T cells, we analyzed the transcription factors T-box expressed in T cells (T-bet) and GATA-3. T-bet, absent in naive gammadelta cells, was induced upon TCR signaling, with IFN-gamma production. T-bet also regulated IL-4 synthesis, as gammadelta cells isolated from T-bet-deficient mice displayed enhanced IL-4 levels with reduced IFN-gamma production. Notably, T-bet expression after TCR signaling in gammadelta cells was not down-regulated by IL-4, in conjunction with a higher ratio of T-bet:GATA-3 expression than that found in CD4+ T cells. Indeed, overexpression of GATA-3 failed to inhibit IFN-gamma secretion in gammadelta cells to the degree seen in CD4(+) T cells. These results indicate that T-bet enhances IFN-gamma secretion and suppresses IL-4 secretion in gammadelta cells, and that GATA-3 fails to counterbalance T-bet-mediated IFN-gamma production, accounting for the default synthesis of IFN-gamma by these T lymphocytes.