Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.

ABSTRACT: Exhausted CD8 T cells (T_EX) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate T_EX cells, but reinvigoration is not durable. A major unanswered question is whether T_EX cells differentiate into functional durable memory T cells (T_MEM) upon antigen clearance. Here, using a mouse model, we found that upon eliminating chronic antigenic stimulation, T_EX cells partially (re)acquire phenotypic and transcriptional features of T_MEM cells. These 'recovering' T_EX cells originated from the T cell factor (TCF-1⁺) T_EX progenitor subset. Nevertheless, the recall capacity of these recovering T

SUBMITTER: Abdel-Hakeem MS 

PROVIDER: S-EPMC8323971 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature