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• W1887732023 abstract "Abstract LPS is a natural adjuvant that potentiates Ag-specific T cell survival and Th1 differentiation by stimulating MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF) signaling pathways. In this study, we reveal the TRIF pathway is critical for amplifying murine effector T cell accumulation into nonlymphoid tissues following immunization with Ag plus LPS. Although LPS increased the accumulation of splenic T cells in TRIF-deficient mice, markedly fewer T cells were recovered from liver and lung in comparison to wild type. Most of the T cells primed in TRIF-deficient mice failed to up-regulate CXCR3 and had an overall reduced capacity to produce IFN-γ, demonstrating effector T cell differentiation was linked to their migration. To investigate the role of TRIF-dependent cytokines, neutralization studies were performed in wild type mice. Although TNF neutralization reduced T cell numbers, its coneutralization with IL-10 unexpectedly restored the T cells, suggesting the balance between pro- and anti-inflammatory cytokines influences T cell survival rather than their magnitude. To investigate a role for costimulatory molecules, we tested whether the T cell defect in TRIF-deficient mice could be corrected with enforced costimulation. Boosting with a CD40 agonist in addition to LPS restored the effector CD8 T cell response in livers of TRIF-deficient mice while only partially restoring CD4 T cells, suggesting that LPS primes CD8 and CD4 T cell immunity through different mechanisms. Overall, our data support targeting TRIF for vaccines aimed to direct immune responses to nonlymphoid tissues." @default.
• W1887732023 created "2016-06-24" @default.
• W1887732023 creator A5021846790 @default.
• W1887732023 creator A5027034727 @default.
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• W1887732023 date "2009-05-01" @default.
• W1887732023 modified "2023-10-03" @default.
• W1887732023 title "Lipopolysaccharide Potentiates Effector T Cell Accumulation into Nonlymphoid Tissues through TRIF" @default.
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• W1887732023 doi "https://doi.org/10.4049/jimmunol.0803616" @default.
• W1887732023 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2947744" @default.
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