regulation of the Il4 and Ifng cytokine genes (15, 16). In contrast, all three Runx proteins are expressed in mature CD8+ T cells (10, 12), and Runx3-deficient CD8+ T cells show reduced cytolytic activity (12, 13). We therefore tested whether Runx3 influenced cytolytic T cell differentiation. In this report, we show that Runx3 and T-box factors synergistically regulate CTL differentiation and function. T-bet is induced quickly upon TCR stimulation and is required for early programming of cytokine production (17), whereas Eomes is induced later during differentiation and sustains IFN-γ expr