Abstract：
BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.
OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
CONCLUSIONS: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.
OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
CONCLUSIONS: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.
摘要：
背景：需要鉴定血管和老年学相关的标记和介质，这些标记和介质可以在生理上将衰老与血管疾病联系起来。有特定T细胞亚群的证据,都受年龄的影响,对血管健康产生积极和消极的影响。CD31+,称为血管生成T细胞，与血管修复有关，而CD28null，称为衰老T细胞，显示促炎和细胞毒性效应子功能。
目的：本研究旨在确定年龄增加和虚弱状态对这些循环CD31+和CD28nullT细胞亚群的联合影响。
方法：这项横断面研究招募了四个不同的男性和女性队列；年轻（20-30岁，n=22),年龄较大（65-75岁，n=17),健壮不脆弱(76岁以上，n=17),和脆弱（76岁以上，n=15）成人。使用FriedFailty方法确定脆弱。基于CD3、CD4、CD8、CD31和CD28的表达,通过全血流式细胞术测定T细胞亚群。认知障碍（CI）通过蒙特利尔认知评估测试进行测量。
结果：无论是以循环计数还是以总T细胞的百分比表示，随着年龄的增长,CD31+T细胞逐渐减少(p<0.05),但与健壮非虚弱组相比,虚弱组有更高的值(p<0.05)。这些变化在CD4+和CD8+部分中相似。与健壮非脆弱组相比，脆弱组的CD28nullT细胞明显更高（p<0.05），包括CD8+(47%对29%，p<0.05)和CD4+(4%vs1%，p<0.05)分数。与mildCI和正常功能相比，中度CI患者的CD28nullT细胞百分比也更高（p<0.05）。
结论：CD8+CD28nullT细胞在衰弱和认知障碍中显著升高，可以作为干预的有用靶标。目前,CD31+T细胞作为衰老生物标志物的应用可能仅限于健康的衰老队列.
目的：本研究旨在确定年龄增加和虚弱状态对这些循环CD31+和CD28nullT细胞亚群的联合影响。
方法：这项横断面研究招募了四个不同的男性和女性队列；年轻（20-30岁，n=22),年龄较大（65-75岁，n=17),健壮不脆弱(76岁以上，n=17),和脆弱（76岁以上，n=15）成人。使用FriedFailty方法确定脆弱。基于CD3、CD4、CD8、CD31和CD28的表达,通过全血流式细胞术测定T细胞亚群。认知障碍（CI）通过蒙特利尔认知评估测试进行测量。
结果：无论是以循环计数还是以总T细胞的百分比表示，随着年龄的增长,CD31+T细胞逐渐减少(p<0.05),但与健壮非虚弱组相比,虚弱组有更高的值(p<0.05)。这些变化在CD4+和CD8+部分中相似。与健壮非脆弱组相比，脆弱组的CD28nullT细胞明显更高（p<0.05），包括CD8+(47%对29%，p<0.05)和CD4+(4%vs1%，p<0.05)分数。与mildCI和正常功能相比，中度CI患者的CD28nullT细胞百分比也更高（p<0.05）。
结论：CD8+CD28nullT细胞在衰弱和认知障碍中显著升高，可以作为干预的有用靶标。目前,CD31+T细胞作为衰老生物标志物的应用可能仅限于健康的衰老队列.
