A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

作者：Xin Gang; Schauder David M; Lainez Begona; Weinstein Jason S; Dai Zhengxi; Chen Yuhong; Esplugues Enric; Wen Renren; Wang Demin; Parish Ian A; Zajac Allan J; Craft Joe; Cui Weiguo^*

来源：Cell Reports, 2015, 13(6): 1118-1124.

DOI：10.1016/j.celrep.2015.09.069

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.

• 出版日期2015-11-10