BATF3 regulates chromatin accessibility during CD8+ T lymphocyte differentiation

CD8+ T lymphocytes differentiate from effector to memory cells following antigen clearance, with prolonged IL-2 production characterizing functional cytotoxic T lymphocytes (CTLs). To identify transcription factors associated with sustained IL-2 production, we compared influenza virus-specific and cytomegalovirus-specific CTLs, identifying Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3) as a key candidate gene. BATF3 overexpression significantly enhanced cell proliferation in both virus-specific CTLs and CD19 chimeric antigen receptor T (CAR-T) cells while reducing cytokine production. ATAC-seq analysis revealed that BATF3 overexpression dynamically regulates chromatin accessibility, affecting diverse cellular processes including cytoskeletal organization, metabolic pathways, and cellular survival signaling. BATF3 specifically facilitated the critical transition from effector to memory phase. These findings establish BATF3 as a master regulator of CD8+ T cell fate determination through dynamic chromatin remodeling mechanisms.