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• W2569359905 abstract "The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69+ CD8 Trm population, including both CD103+ and CD103− cells. These T-cell responses persist to greater than 200 days post-boost and protect against lethal influenza challenge in aged (year old) mice. The expansion of the nucleoprotein-specific CD8 Trm population during boosting involves recruitment of circulating antigen-specific cells and is critically dependent on local rather than systemic administration of 4-1BBL as well as on 4-1BB on the CD8 T cells. Moreover, during primary influenza infection of mixed bone marrow chimeras, 4-1BB-deficient T cells fail to contribute to the lung-resident Trm population. These findings establish both endogenous and supraphysiological 4-1BBL as a critical regulator of lung-resident memory CD8 T cells during influenza infection." @default.
• W2569359905 created "2017-01-13" @default.
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• W2569359905 date "2017-09-01" @default.
• W2569359905 modified "2023-10-16" @default.
• W2569359905 title "Intrinsic 4-1BB signals are indispensable for the establishment of an influenza-specific tissue-resident memory CD8 T-cell population in the lung" @default.
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• W2569359905 doi "https://doi.org/10.1038/mi.2016.124" @default.
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• W2569359905 hasPublicationYear "2017" @default.
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