Stat5 opposes the transcription factor Tox and rewires exhausted CD8⁺ T cells toward durable effector-like states during chronic antigen exposure.

ABSTRACT: Rewiring exhausted CD8⁺ T (Tex) cells toward functional states remains a therapeutic challenge. Tex cells are epigenetically programmed by the transcription factor Tox. However, epigenetic remodeling occurs as Tex cells transition from progenitor (Tex^prog) to intermediate (Tex^int) and terminal (Tex^term) subsets, suggesting development flexibility. We examined epigenetic transitions between Tex cell subsets and revealed a reciprocally antagonistic circuit between Stat5a and Tox. Stat5 directed Tex^int cell formation and re-instigated partial effector biology during this Tex^prog-to-Tex^int cell transition. Constitutive Stat5a activity antagonized Tox and rewired CD8⁺ T cells from exhaustion to a durable eff

SUBMITTER: Beltra JC 

PROVIDER: S-EPMC10752292 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature