The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells

Nat Immunol. 2014 Apr;15(4):373-83. doi: 10.1038/ni.2834. Epub 2014 Mar 2.


The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells showed profound defects in effector population expansion and underwent proliferative and metabolic catastrophe early after encountering antigen. BATF, together with the transcription factors IRF4 and Jun proteins, bound to and promoted early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors while paradoxically repressing genes encoding effector molecules (IFN-γ and granzyme B). Thus, BATF amplifies T cell antigen receptor (TCR)-dependent expression of transcription factors and augments the propagation of inflammatory signals but restrains the expression of genes encoding effector molecules. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.

Publication types

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

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Growth Processes / genetics
  • Cells, Cultured
  • Down-Regulation
  • Granzymes / genetics
  • Granzymes / metabolism
  • Interferon Regulatory Factors / metabolism
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-jun / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Th17 Cells / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics


  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Interferon Regulatory Factors
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-jun
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • interferon regulatory factor-4
  • Interferon-gamma
  • Positive Regulatory Domain I-Binding Factor 1
  • Granzymes

Associated data

  • GEO/GSE54191
  • GEO/GSE54215