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- W4313341502 abstract "Abstract PD1-PD-L1 is a costimulatory pathway that regulates self-tolerance by providing negative signals to T cells, resulting in anergy and decreased cytotoxicity. We have shown that induction of suppressive CD8+ T cells (CD8+Ti) reduces PD-1 expression on suppressor cells, which links to increased Foxp3 and TGF-£] expression. These induced CD8+Ti suppress proliferation of CD4+CD25- T cells; however, suppression is abrogated by silencing of PD-1. In untreated mice, the number and percentage of CD8+Ti in PBMC decreased over time, with increased PD-1. Blocking PD-1 increased TGF-ƒÒ expression and decreased anti-DNA and total IgG production Untreated mice developed >2+ proteinuria at week 30, and began to expire at week 39. Yet, mice treated with anti-PD-1 Ab had <2+ proteinuria until 45 weeks old, and survival was 100% until 50 weeks old. PD-1 is likely one of the core participants in inherent autoreactivity of CD8+Ti and in the mechanisms of immune tolerance in our model. Blocking PD-1 in untreated mice delays autoantibody production and nephritis for weeks. TGF£] up-regulation suggests that blocking PD-1 may affect on CD8+ T cell suppression by TGF£] secretion. However, PD-1 abrogation 1 prevents the suppressive capacity of tolerized CD8+Ti. Downregulation may be needed to release the inhibitory capacity of the cells to permit full generation of inhibitory and cytotoxic CD8+ T cells. PD-1 expression has to be finely tuned to enable CD8+Ti to control autoimmunity." @default.
- W4313341502 created "2023-01-06" @default.
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- W4313341502 date "2009-04-01" @default.
- W4313341502 modified "2023-10-18" @default.
- W4313341502 title "Altered PD-1-PD-L1 Pathway in CD8+ T cells of (New Zealand Black x New Zealand White) BWF1 Mice with Anti-PD-1 antibody (99.29)" @default.
- W4313341502 doi "https://doi.org/10.4049/jimmunol.182.supp.99.29" @default.
- W4313341502 hasPublicationYear "2009" @default.
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