The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age
The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age
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DOI：
10.1111/j.1365-2249.2005.02798.x
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发表时间：
2005-06-01
影响因子：
4.6
通讯作者：
Moss, PA
中科院分区：
文献类型：
--
作者：
Gregg, R;Smith, CM;Moss, PA
老龄化与免疫缺陷和失调的证据有关。免疫系统随衰老的关键变化包括与胸腺退化和寡克隆记忆T细胞的外周扩增相关的幼稚T细胞输出的进行性减少。这些特征与体外和体内免疫应答受损的证据相关，称为免疫衰老。CD 4（+）CD 25（+）T细胞最近被认为是外周免疫调节的介质，并在控制自身免疫和病原体特异性免疫应答中发挥作用。CD 4（+）CD 25（+）调节性T细胞在免疫衰老中的意义尚不清楚。我们研究了不同年龄段健康志愿者中CD 4（+）CD 25（+）T细胞的数量、表型和功能。我们证明了健康志愿者中CD 4（+）CD 25（+）和CD 4（+）CD 25（high）T细胞的数量随着年龄的增长而增加。在两个年龄组中，CD 4（+）CD 25（+）T细胞显示出与调节性T细胞一致的表型。对年轻和老年供体中的CD 4（+）CD 25（高）T细胞的进一步分析显示，细胞内CTLA-4的表达和活化标志物的表面表达相等。在体外，CD 4（+）CD 25（高）T细胞的功能滴定试验表明，在年轻和老年供体中具有相同的调节功能，抑制多克隆T细胞刺激后的增殖和细胞因子产生。这些观察结果表明，外周血CD 4（+）CD 25（高）调节性T细胞的增加与衰老有关。这些扩增的细胞与老年人免疫衰老的相关性尚不清楚。
Ageing is associated with evidence of immune deficiency and dysregulation. Key changes in the immune system with ageing include a progressive reduction in naive T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. These features are associated with evidence of impaired immune responsiveness both in vitro and in vivo, termed immune senescence. CD4(+) CD25(+) T cells have recently been recognized as mediators of peripheral immune regulation and play a role in the control of autoimmune and pathogen-specific immune responses. The significance of CD4(+) CD25(+) regulatory T cells in the context of immunosenescence is not known. We have investigated the number, phenotype and function of CD4(+) CD25(+) T cells in healthy volunteers over a wide age range. We demonstrate that the number of CD4(+) CD25(+) and CD4(+) CD25(high) T cells in healthy volunteers increases with age. In both age groups CD4(+) CD25(+) T cells showed a phenotype consistent with that described for regulatory T cells. Further analysis of CD4(+) CD25(high) T cells in young and elderly donors showed equivalent expression of intracellular CTLA-4 and surface expression of activation markers. In vitro, functional titration assays of CD4(+) CD25(high) T cells demonstrated equivalent regulatory function in both young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. These observations demonstrate an increase in peripheral blood CD4(+) CD25(high) regulatory T cells associated with ageing. The relevance of these expanded cells in relation to the immune senescence seen in the elderly as yet remains unclear.