CD8 T-cell immune phenotype of successful aging

CD8 T-cell immune phenotype of successful aging
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DOI:
10.1016/j.mad.2005.10.001
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发表时间:
2006-03-01
影响因子:
5.3
通讯作者:
Mountz, JD
Mountz, JD
中科院分区:
医学3区
文献类型:
--
作者:
Hsu, HC;Scott, DK;Mountz, JD

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根据定义,90岁人口代表已证明成功老化的个人。我们通过分析CD 28和Fas(CD 95)的表达,以及分析活化和活化诱导的细胞死亡(AICD)来确定90岁以上的CD 8(+)T细胞衰老的状态。从三组受试者中分离外周血单核细胞(PBMC):成人(20-64岁)、老年人(65-89岁)和90岁以上(>= 90岁)。用植物血凝素(PHA)(10 μ g/ml)刺激PBMC。用对CD 4、CD 8、CD 28、CD 45 RO和Fas特异性的缀合抗体标记细胞,并通过FACS((R))分析。CD 28(+)Fas(-)CD 8(+)T细胞的百分比与体外刺激前每个个体的年龄呈强负相关(R-2 = 0.76,p < 0.000 1)。与其他与CD 8(+)T细胞衰老相关的生物标志物(CD 28(-)、CD 28(-)CD 45 RO(+)和Fas(+))相比,CD 28(+)Fas(-)CW 8(+)-细胞群的丧失表现出与个体的实际年龄最强的相关性。在PHA刺激后,在第3天,来自≥ 65岁的个体的同时表达CD 28(+)和Fas(+)的CD 8(+)T细胞的百分比降低。令人惊讶的是,在第7天,90岁以上的CD 8(+)T细胞的AICD反应高于其他两组。这些结果表明,成功的衰老并不能阻止未受刺激的CD 8(+)T细胞衰老表型的发展,但与CD 8(+)T细胞功能的保留有关,包括活化和AICD。AICD增加可能导致T细胞的年轻化能力增强,并限制老化对90岁以上T细胞功能的影响。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The nonagenarian Population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8(+) T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood rnononuclear cells (PBMCs) were isolated from three groups of Subjects: adults (20-64-year-old), older adults (65-89-year-old),and nonagenarians(>= 90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA)(10 mu g/ml). The cells were labeled with conjugated antibodies specific for CD4,CD8, CD28, CD45RO, and Fas, and were analyzed by FACS((R)). There was a strong negative correlation of the percentage of CD28(+)Fas(-) CD8(+) T-cells with the age of each individual prior to stimulation in vitro (R-2 = 0.76, p < 0.000 1). Compared to other biomarkers (CD28(-), CD28(-)CD45RO(+), and Fas(+)) that have been associated with CD8(+) T-cell aging, the loss of the CD28(+) Fas(-) CW8(+)-cell population exhibited the strongest correlation With the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8(+) T-cells from individual >= 65-year-old that expresses both CD28(+) and Fas(+) at day 3. Surprisingly, the AICD response of CD8(+) T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results Suggest that successful aging does not prevent development of the senescent phenotype Of unstimulated CD8(+) T cells, but is associated with preservation of CD8(+) T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians. (c) 2005 Elsevier Ireland Ltd. All rights reserved.