Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype

Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype
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DOI:
10.1093/intimm/dxm151
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发表时间:
2008-03-01
影响因子:
4.4
通讯作者:
Nanan, Ralph
Nanan, Ralph
中科院分区:
医学3区
文献类型:
--
作者:
Santner-Nanan, Brigitte;Seddiki, Nabila;Nanan, Ralph

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我们和其他人最近描述了一种通过表面表型CD 4(+)CD 127(lo)CD 25(+)分离活叉头boxp 3(FoxP 3(+))T调节细胞(TcR)的方法。在这项研究中,我们使用新的策略来测量不同年龄的Treg数量,表型和功能。CD 4(+)CD 127(lo)CD 25(+)T淋巴细胞的平均百分比在整个生命过程中仅略有增加,从脐带血中的6.10%增加到20 - 25岁成人PBMC中的7.22%和60岁以上成人PBMC中的7.50%。在所有年龄组中,与CD 4(+)Foxp 3(-)常规T细胞相比,获得CD 45 RA(-)记忆表型的T细胞比例更高。这种增加完全归因于具有效应记忆表型的T细胞的增加,而中枢记忆表型细胞在Treg和常规CD 4(+)T细胞群中是不对称的。CD 95的表达在所有年龄段的T细胞和传统的CD 4(+)T细胞之间也有差异。然而,不同的幼稚和记忆Treg亚群的抑制能力没有差异。这些结果表明,与传统的CD 4(+)T细胞相比,TcB经历了从幼稚到效应记忆表型的优先分化,这是由其对自身抗原而不是外来抗原的特异性驱动的。然而,数量和功能在整个生命过程中非常稳定。
We and others recently described a method for isolating viable forkhead boxp3 (FoxP3(+)) T regulatory cells (Tregs) by means of the surface phenotype CD4(+)CD127(lo)CD25(+). In this study, we used the new strategy to measure Treg numbers, phenotype and function at different ages. Mean percentages of CD4(+)CD127(lo)CD25(+) Tregs increased only slightly throughout life, from 6.10% in cord blood to 7.22% in PBMC from adults between 20 and 25 years and 7.50% in PBMC from adults over the age of 60. In all age groups, a higher proportion of Tregs had acquired a CD45RA(-) memory phenotype compared with CD4(+)Foxp3(-) conventional T cells. This increase was entirely attributable to increased Tregs with an effector memory phenotype, whereas central memory phenotype cells were comparably represented within the Treg and conventional CD4(+) T-cell populations. Expression of CD95 also differed between Tregs and conventional CD4(+) T cells at all ages. However there was no difference in the suppressive capacity of the different naive and memory Treg subsets. These results suggest that, compared with their conventional CD4(+) T-cell counterparts, Tregs undergo preferential differentiation from a naive to an effector memory phenotype, driven by their specificity for self- rather than foreign antigen. However, number and function are remarkably stable throughout life.