CD45RA-Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA-CD27+CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis

CD45RA-Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA-CD27+CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis
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DOI:
10.1016/j.bbrc.2013.05.120
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发表时间:
2013-09-06
影响因子:
3.1
通讯作者:
Morinobu, Akio
Morinobu, Akio
中科院分区:
生物学4区
文献类型:
--
作者:
Matsuki, Fumichika;Saegusa, Jun;Morinobu, Akio

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人CD4 + T细胞可分为幼稚、中枢记忆(T-CM)或效应记忆(T-EM)细胞。为了确定类风湿关节炎(RA)发病机制中最重要的CD4 + T细胞亚群,我们将人CD4 + T细胞表型定义为功能不同的亚群,并分析了每个亚群在外周血中的分布和特征。我们根据CD45RA、CCR7、CD27和CD28的表达将CD4 + T细胞分为六个新的亚群。与健康对照相比,RA患者中CCR 7 + CD 45 RA-CD 27 + CD 28 + T-CM亚群中CD 4 + T细胞的比例显着较小。在RA中,CCR7-CD45RA-CD27 + CD28 + T-EM亚群中产生TNF-α的细胞的频率显著增加。此外,在RA患者外周血中减少的CCR7 + CD45RA-CD27 + CD28 + T-CM亚群中,总Foxp3 + Treg细胞和CD45RA-Foxp3(高)活化/效应Treg细胞的比例显著降低。我们的研究结果表明,在特定亚群中,TNF-α产生细胞比例的增加和CD45RA-Foxp3(高)活化/效应Treg细胞比例的降低可能在RA的发病机制中起关键作用。(C)2013 Elsevier Inc. All rights reserved.
Human CD4+ T cells can be classified as either naive, central memory (T-CM), or effector memory (T-EM) cells. To identify the CD4+ T cell subsets most important in the pathogenesis of rheumatoid arthritis (RA), we phenotypically defined human CD4+ T cells as functionally distinct subsets, and analyzed the distribution and characteristics of each subset in the peripheral blood. We classified CD4+ T cells into six novel subsets based on the expression of CD45RA, CCR7, CD27, and CD28. The CCR7 + CD45RA-CD27 + CD28+ T-CM subset comprised a significantly smaller proportion of CD4+ T cells in RA patients compared to healthy controls. The frequency of TNF-alpha-producing cells in the CCR7-CD45RA-CD27 + CD28+ T-EM subset was significantly increased in RA. Furthermore, within the CCR7 + CD45RA-CD27 + CD28+ T-CM subset, which was decreased in periperal blood from RA, the proportions of total Foxp3+ Treg cells and CD45RA-Foxp3(high) activated/effector Treg cells were significantly lower in RA patients. Our findings suggest that the increased proportion of TNF-alpha-producing cells and the decreased proportion of CD45RA-Foxp3(high) activated/effector Treg cells in particular subsets may have critical roles in the pathogenesis of RA. (C) 2013 Elsevier Inc. All rights reserved.