1. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control
- Author
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Xin, Gang, Schauder, David M., Lainez, Begona, Weinstein, Jason S., Dai, Zhengxi, Chen, Yuhong, Esplugues, Ennric, Wen, Renren, Wang, Demin, Parish, Ian, Zajac, Allan J., Craft, Joe, Cui, Weiguo, Xin, Gang, Schauder, David M., Lainez, Begona, Weinstein, Jason S., Dai, Zhengxi, Chen, Yuhong, Esplugues, Ennric, Wen, Renren, Wang, Demin, Parish, Ian, Zajac, Allan J., Craft, Joe, and Cui, Weiguo
- Abstract
Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue "unhelped" CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells "help" the CD8 response during chronic infection via IL-21-induced BATF expression. Xin et al. identify a pathway that connects CD4-derived IL-21 to a BATF-mediated transcriptional program in CD8 T cells, which plays a key role in the sustained effector function of CD8 T cells during chronic viral infection.
- Published
- 2015