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• W4386157281 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 reduce the Tpex pool. Together, these findings demonstrate that continuous CD28 engagement is needed to sustain PD-1 + CD8 T cells and suggest that increasing CD28 signaling promotes Tpex differentiation into more functional effector-like Tex, possibly without compromising long-term responses." @default.
• W4386157281 created "2023-08-26" @default.
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• W4386157281 date "2023-08-04" @default.
• W4386157281 modified "2023-10-06" @default.
• W4386157281 title "Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1 ⁺ PD-1 ⁺ CD8 T cells" @default.
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• W4386157281 doi "https://doi.org/10.1126/sciimmunol.adg0878" @default.
• W4386157281 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37624910" @default.
• W4386157281 hasPublicationYear "2023" @default.
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