Batf3 programs CD8 T cell memory

Anti-viral 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 (cDC1), which in turn are critical for the optimal priming of CD8 T cells. Here we show that BATF3 is expressed within the first days after priming but has long-lasting T cell intrinsic effects. We found that T cells that lack Batf3 show a 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 regulates 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. Overall design: CD8+ T cells were isolated from spleen of either WT or Batf3-/- mice. Splenocytes were enriched for CD8 T cells and cultured for either 48h or 72h in supplemented medium with IL-15 (50ng/ml) plus anti-CD3/CD28 (1µg/ml). Four technical replicates from each condition were used for the bulk sequencing.