Yao, ShuyuBuzo, Bruno Fernando d.Pham, DuyJiang, LiTaparowsky, Elizabeth J.Kaplan, Mark H.Sun, Jie2015-09-142015-09-142013-11-14Yao, S., Buzo, B. F. d., Pham, D., Jiang, L., Taparowsky, E. J., Kaplan, M. H., & Sun, J. (2013). Interferon regulatory factor 4 sustains CD8+ T cell expansion and effector differentiation. Immunity, 39(5), 10.1016/j.immuni.2013.10.007. http://doi.org/10.1016/j.immuni.2013.10.007https://hdl.handle.net/1805/6851Upon infection, CD8(+) T cells undergo a stepwise process of early activation, expansion, and differentiation into effector cells. How these phases are transcriptionally regulated is incompletely defined. Here, we report that interferon regulatory factor 4 (IRF4), dispensable for early CD8(+) T cell activation, was vital for sustaining the expansion and effector differentiation of CD8(+) T cells. Mechanistically, IRF4 promoted the expression and function of Blimp1 and T-bet, two transcription factors required for CD8(+) T cell effector differentiation, and simultaneously repressed genes that mediate cell cycle arrest and apoptosis. Selective ablation of Irf4 in peripheral CD8(+) T cells impaired antiviral CD8(+) T cell responses, viral clearance, and CD8(+) T cell-mediated host recovery from influenza infection. IRF4 expression was regulated by T cell receptor (TCR) signaling strength via mammalian target of rapamycin (mTOR). Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responseen-USPublisher PolicyT cell receptorsArticle