Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1⁺ PD-1⁺ CD8 T cells.

ABSTRACT: During persistent antigen stimulation, such as in chronic infections and cancer, CD8 T cells differentiate into a hypofunctional programmed death protein 1-positive (PD-1⁺) exhausted state. Exhausted CD8 T cell responses are maintained by precursors (Tpex) that express the transcription factor T cell factor 1 (TCF-1) and high levels of the costimulatory molecule CD28. Here, we demonstrate that sustained CD28 costimulation is required for maintenance of antiviral T cells during chronic infection. Low-level CD28 engagement preserved mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation into TCF-1^neg exhausted CD8 T cells (Tex). Furthermore, enhanced differentiation by CD28 engagement did not

SUBMITTER: Humblin E 

PROVIDER: S-EPMC10805182 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature