# BATF and BATF3 deficiency alters CD8+ effector/exhausted T cells balance in skin transplantation

## TL;DR

This study shows that lacking BATF and BATF3 proteins in CD8+ T cells reduces their activity and improves skin transplant survival in mice.

## Contribution

The study reveals a novel role of BATF and BATF3 in regulating CD8+ T cell differentiation and exhaustion in the context of transplantation.

## Key findings

- BATF and BATF3 deficiency promotes long-term survival of skin allografts.
- Deficiency in BATF and BATF3 reduces CD8+ T cell allo-response and cytokine secretion.
- BATF and BATF3 deficiency leads to the generation of exhausted CD8+ T cells.

## Abstract

It is well-established that CD8+ T-cells play a critical role in graft rejection. The basic leucine zipper ATF-like transcription factor (BATF) and BATF3 are transcriptional factors expressed in T lymphocytes. Herein, we investigated the functions of BATF and BATF3 in the differentiation and exhaustion of CD8+ T cells following alloantigen activation.

Wild-type CD8+ T cells, BATF-deficient (Batf−/−) CD8+ T cells, and CD8+ T cells deficient in both BATF and BATF3 (Batf−/−Batf3−/−) were transferred to B6.Rag1−/− mice, which received skin allografts from BALB/c mice. Flow cytometry was conducted to investigate the number of CD8+ T cells and the percentage of effector subsets.

BATF expression positively correlated with effector CD8+ T cell differentiation. BATF and BATF3 deficiency promoted skin allograft long-term survival and attenuated the CD8+ T cell allo-response and cytokine secretion. Finally, BATF and BATF3 deficiency prompted the generation of exhausted CD8+ T cells.

Overall, our findings provide preliminary evidence that both BATF and BATF3 deficiency influences the differentiation of effector CD8+ T cells and mediates the exhaustion of CD8+ T cells, prolonging transplant survival. Targeting BATF and BATF3 to inhibit CD8+ T cell function has huge prospects for application as a therapeutic approach to prevent transplant rejection.

The online version contains supplementary material available at 10.1186/s10020-024-00792-0.