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

Cell Rep. 2015 Nov 10;13(6):1118-1124. doi: 10.1016/j.celrep.2015.09.069. Epub 2015 Oct 29.


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.

Keywords: BATF; Blimp-1; CD8 T cell; IL-21; IRF4; LCMV; STAT3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Interferon Regulatory Factors / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Positive Regulatory Domain I-Binding Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Virus Diseases / immunology*


  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Interferon Regulatory Factors
  • Interleukins
  • Prdm1 protein, mouse
  • Transcription Factors
  • interferon regulatory factor-4
  • Positive Regulatory Domain I-Binding Factor 1
  • interleukin-21