| First Author | Yao S | Year | 2013 |
| Journal | Immunity | Volume | 39 |
| Issue | 5 | Pages | 833-45 |
| PubMed ID | 24211184 | Mgi Jnum | J:208994 |
| Mgi Id | MGI:5565532 | Doi | 10.1016/j.immuni.2013.10.007 |
| Citation | Yao S, et al. (2013) Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity 39(5):833-45 |
| abstractText | 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 responses. |
