BATF targets T cell exhaustion for termination

Abstract

New reports glean further insight into the role of the transcription factor BATF in pivoting the differentiation of CD8⁺ T cells away from undergoing T cell exhaustion and facilitating transition of these cells into potent effectors.

Figure 1.. CD8⁺ Effector T cell differentiation in chronic diseases.

Seo et al. demonstrate that BATF cooperates with IRF4 to skew CAR-T cells away from a T cell exhaustion lineage and towards an effector T cell (① Effector [Teff]) subset which results in enhanced tumoral control. This Teff subset, or similar population, has also been observed within the early stage of chronic lymphocytic choriomeningitis virus (LCMV) infection^, . Chen et al. determined that BATF, and, in part, T-bet, are required for the differentiation of Ly108⁺ T progenitor exhausted-like subset (Tpex) into CX₃CR1⁺ subset (② Teff-like) at the late phase of chronic LCMV infection (>20 days post infection [dpi]). CX₃CR1⁺ cells (③ Teff-like) have been described previously as a transitory exhausted T cell subset which gives rise to terminally exhausted T cells (Tex) in mice infected with chronic LCMV with constant viral load (>45 dpi). Chen at al. also provides evidence for BATF’s role in chromatin remodeling of effector-associated gene loci including Tbx21 and Klf2 to foster T cell effector function. (Figure created with BioRender.com).