Persistence of self-reactive CD8+ T cells in the CNS requires TOX-dependent chromatin remodeling.

ABSTRACT: Self-reactive CD8⁺ T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we characterize the transcriptional and epigenetic landscape of self-reactive CD8⁺ T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8⁺ T cells emerging from acute viral infection. We find that autoimmune CD8⁺ T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling. This self-reactive CD8⁺ T cell fate depends on the transcriptional regulation by the DNA-binding HMG-box protein TOX

SUBMITTER: Page N 

PROVIDER: S-EPMC7881115 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature