tetano
Editor, Senior Moderator
Immunity. 2013 Nov 6. pii: S1074-7613(13)00466-4. doi: 10.1016/j.immuni.2013.10.007. [Epub ahead of print]
Interferon Regulatory Factor 4 Sustains CD8+ T Cell Expansion and Effector Differentiation.
Yao S, Buzo BF, Pham D, Jiang L, Taparowsky EJ, Kaplan MH, Sun J.
Source
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Abstract
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.
Copyright ? 2013 Elsevier Inc. All rights reserved.
PMID:
24211184
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24211184
Interferon Regulatory Factor 4 Sustains CD8+ T Cell Expansion and Effector Differentiation.
Yao S, Buzo BF, Pham D, Jiang L, Taparowsky EJ, Kaplan MH, Sun J.
Source
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Abstract
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.
Copyright ? 2013 Elsevier Inc. All rights reserved.
PMID:
24211184
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24211184