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• W4285891189 endingPage "104179" @default.
• W4285891189 startingPage "104179" @default.
• W4285891189 abstract "BackgroundImmunosenescence (ISC) describes age-related changes in immune-system composition and function. Multiple sclerosis (MS) is a lifelong inflammatory condition involving effector and regulatory T-cell imbalance, yet little is known about T-cell ISC in MS. We examined age-associated changes in circulating T cells in MS compared to normal controls (NC).MethodsForty untreated MS (Mean Age 43·3, Range 18–72) and 49 NC (Mean Age 48·6, Range 20–84) without inflammatory conditions were included in cross-sectional design. T-cell subsets were phenotypically and functionally characterized using validated multiparametric flow cytometry. Their aging trajectories, and differences between MS and NC, were determined using linear mixed-effects models.FindingsMS patients demonstrated early and persistent redistribution of naïve and memory CD4 T-cell compartments. While most CD4 and CD8 T-cell aging trajectories were similar between groups, MS patients exhibited abnormal age-associated increases of activated (HLA-DR+CD38+; (P = 0·013) and cytotoxic CD4 T cells, particularly in patients >60 (EOMES: P < 0·001). Aging MS patients also failed to upregulate CTLA-4 expression on both CD4 (P = 0·014) and CD8 (P = 0·009) T cells, coupled with abnormal age-associated increases in frequencies of B cells expressing costimulatory molecules.InterpretationWhile many aspects of T-cell aging in MS are conserved, the older MS patients harbour abnormally increased frequencies of CD4 T cells with activated and cytotoxic effector profiles. Age-related decreased expression of T-cell co-inhibitory receptor CTLA-4, and increased B-cell costimulatory molecule expression, may provide a mechanism that drives aberrant activation of effector CD4 T cells that have been implicated in progressive disease.FundingStated in Acknowledgements section of manuscript." @default.
• W4285891189 created "2022-07-20" @default.
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• W4285891189 date "2022-08-01" @default.
• W4285891189 modified "2023-10-12" @default.
• W4285891189 title "Immune aging in multiple sclerosis is characterized by abnormal CD4 T cell activation and increased frequencies of cytotoxic CD4 T cells with advancing age" @default.
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• W4285891189 doi "https://doi.org/10.1016/j.ebiom.2022.104179" @default.
• W4285891189 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35868128" @default.
• W4285891189 hasPublicationYear "2022" @default.
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