BATF3 programs CD8+ T cell memory

Nat Immunol. 2020 Nov;21(11):1397-1407. doi: 10.1038/s41590-020-0786-2. Epub 2020 Sep 28.


Antiviral CD8+ T cell responses are characterized by an initial activation/priming of T lymphocytes followed by a massive proliferation, subset differentiation, population contraction and the development of a stable memory pool. The transcription factor BATF3 has been shown to play a central role in the development of conventional dendritic cells, which in turn are critical for optimal priming of CD8+ T cells. Here we show that BATF3 was expressed transiently within the first days after T cell priming and had long-lasting T cell-intrinsic effects. T cells that lacked Batf3 showed normal expansion and differentiation, yet succumbed to an aggravated contraction and had a diminished memory response. Vice versa, BATF3 overexpression in CD8+ T cells promoted their survival and transition to memory. Mechanistically, BATF3 regulated T cell apoptosis and longevity via the proapoptotic factor BIM. By programing CD8+ T cell survival and memory, BATF3 is a promising molecule to optimize adoptive T cell therapy in patients.

Publication types

  • 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*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cell Survival / genetics
  • Cellular Reprogramming / genetics*
  • Gene Expression
  • Humans
  • Immunologic Memory / genetics*
  • Immunophenotyping
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • BATF3 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Repressor Proteins
  • Transcription Factors