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• W1668771408 endingPage "874" @default.
• W1668771408 startingPage "865" @default.
• W1668771408 abstract "With increasing age, naive CD4 T cells acquire intrinsic defects that compromise their ability to respond and differentiate. Type I IFNs, pervasive constituents of the environment in which adaptive immune responses occur, are known to regulate T cell differentiation and survival. Activated naive CD4 T cells from older individuals have reduced responses to type I IFN, a defect that develops during activation and that is not observed in quiescent naive CD4 T cells. Naive CD4 T cells from young adults upregulate the expression of STAT1 and STAT5 after activation, lowering their threshold to respond to type I IFN stimulation. The heightened STAT signaling is critical to maintain the expression of CD69 that regulates lymphocyte egress and the ability to produce IL-2 and to survive. Although activation of T cells from older adults also induces transcription of STAT1 and STAT5, failure to exclude SHP-1 from the signaling complex blunts their type I IFN response. In summary, our data show that type I IFN signaling thresholds in naive CD4 T cells after activation are dynamically regulated to respond to environmental cues for clonal expansion and memory cell differentiation. Naive CD4 T cells from older adults have a defect in this threshold calibration. Restoring their ability to respond to type I IFN emerges as a promising target to restore T cell responses and to improve the induction of T cell memory." @default.
• W1668771408 created "2016-06-24" @default.
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• W1668771408 creator A5056587089 @default.
• W1668771408 creator A5063946809 @default.
• W1668771408 creator A5073400005 @default.
• W1668771408 date "2015-08-01" @default.
• W1668771408 modified "2023-10-09" @default.
• W1668771408 title "Age-Associated Failure To Adjust Type I IFN Receptor Signaling Thresholds after T Cell Activation" @default.
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• W1668771408 doi "https://doi.org/10.4049/jimmunol.1402389" @default.
• W1668771408 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4506866" @default.
• W1668771408 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26091718" @default.
• W1668771408 hasPublicationYear "2015" @default.
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