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- W4313405612 abstract "Abstract Effective peripheral T cell responses rely upon a diverse T cell repertoire, which is generated during the process of thymic selection. Signaling through the T cell receptor is critical in determining the lineage fate of developing thymocytes; however, it has been established that costimulatory molecules and cytokines can also contribute to fate decisions. Interestingly, coinhibitory molecules, such as programmed cell death protein 1 (PD-1), and their ligands are also expressed in the thymus. Expression of these molecules early in T cell development could regulate lineage fate decisions; however, their potential role in modulating T cell selection is not well-understood. We demonstrate that PD-1 is differentially expressed throughout thymocyte development. Additionally, we show that PD-1’s ligands, PD-L1 and PD-L2, are expressed by thymic epithelial cells. To elucidate the role of PD-1 signaling in regulating T cell selection, we examined mice deficient in PD-1 or PD-L1. Disrupting PD-1 signaling results in an increase in regulatory T cells (Tregs), but not other agonistly selected cell populations. This effect is dose-dependent as mice heterozygous for PD-1 or PD-L1 display an intermediate phenotype. Interestingly, our data suggest that PD-1’s regulation of Treg development is not through its inhibition of T cell receptor signaling, but rather through regulation of IL-2 cytokine production. These data demonstrate that PD-1 signaling restricts Treg development in the thymus, which broadens our understanding of the role of inhibitory proteins to include regulation of T cell development. Supported by grants from NSF (GRFP AVPRS0015) and NIH (F31 CA261058-01)." @default.
- W4313405612 created "2023-01-06" @default.
- W4313405612 creator A5026868461 @default.
- W4313405612 creator A5049077444 @default.
- W4313405612 date "2022-05-01" @default.
- W4313405612 modified "2023-09-25" @default.
- W4313405612 title "A lineage specific role for PD-1 in agonist selection in the thymus" @default.
- W4313405612 doi "https://doi.org/10.4049/jimmunol.208.supp.107.07" @default.
- W4313405612 hasPublicationYear "2022" @default.
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