Animal study demonstrates that BATF and BATF3 deficiency shifts CD8+ T cells toward exhaustion and extends skin graft survival in mice, suggesting a novel target to prevent transplant rejection.
Background 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. Methods Wild-type CD8 + T cells, BATF-deficient ( Batf −/− ) CD8 + T cells, and CD8 + T cells deficient in both BATF and BATF3 ( Batf −/− Batf 3 −/− ) 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. Results 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. Conclusions 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.
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Li et al. (2024) studied this question.
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