Browsing by Author "Buzo, Bruno Fernando d."

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    Interferon regulatory factor 4 sustains CD8+ T cell expansion and effector differentiation
    (Elsevier, 2013-11-14) Yao, Shuyu; Buzo, Bruno Fernando d.; Pham, Duy; Jiang, Li; Taparowsky, Elizabeth J.; Kaplan, Mark H.; Sun, Jie; Pediatrics, School of Medicine
    Upon 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 response