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

ABSTRACT

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-/-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. 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.