The CD8⁺ T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.

ABSTRACT: Peripheral CD8⁺ T cell tolerance is a checkpoint in both autoimmune disease and anti-cancer immunity. Despite its importance, the relationship between tolerance-induced states and other CD8⁺ T cell differentiation states remains unclear. Using flow cytometric phenotyping, single-cell RNA sequencing (scRNA-seq), and chromatin accessibility profiling, we demonstrated that in vivo peripheral tolerance to a self-antigen triggered a fundamentally distinct differentiation state separate from exhaustion, memory, and functional effector cells but analogous to cells defectively primed against tumors. Tolerant cells diverged early and progressively from effector cells, adopting a transcriptionally and epigenetically distinct state within 60 h of antigen encounter. Breaching tol

SUBMITTER: Van Der Byl W 

PROVIDER: S-EPMC11807353 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature