Abdulahad Wayel H, Stegeman Coen A, van der Geld Ymke M, Doornbos-van der Meer Berber, Limburg Pieter C, Kallenberg Cees G M
University Medical Center Groningen, Groningen, The Netherlands.
Arthritis Rheum. 2007 Jun;56(6):2080-91. doi: 10.1002/art.22692.
Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25(high) and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed.
Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25(high),CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls.
In WG patients, a significant increase was observed in the percentage of circulating CD25(high),CD4+ and CD25(low),CD4+ T cells, whereas CD25-,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25(high),FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25(high),CD4+ T cells was tested, CD25(high),CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells.
These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis.
越来越多的数据支持调节性T细胞（CD4+T细胞的一个亚群，表达CD25（高）和转录因子叉头框P3（FoxP3））在控制和预防自身免疫中所起的作用。在韦格纳肉芽肿（WG），一种自身免疫性血管炎中，即使在缓解期患者中，也观察到循环CD4+T细胞上CD25的上调。本研究的目的是检测缓解期WG患者中调节性T细胞的频率和/或功能是否受到干扰。
从52例缓解期WG患者以及27例年龄和性别匹配的健康对照者中新鲜分离外周血单个核细胞。使用CD4、CD25、FoxP3和CD45RO标记物通过流式细胞术评估循环调节性T细胞的比例。在10例缓解期WG患者和10例年龄和性别匹配的健康对照者中，使用多克隆刺激剂和共培养试验确定CD25（高）、CD4+T细胞的无反应性和抑制功能。
与健康对照者相比，在WG患者中，循环CD25（高）、CD4+和CD25（低）、CD4+T细胞的百分比显著增加，而CD25-、CD4+T细胞减少。在循环CD4+T细胞中，WG患者中具有记忆表型的调节性T细胞（CD25（高）、FoxP3+）百分比增加。然而，当检测CD25（高）、CD4+T细胞的抑制功能时，WG患者的CD25（高）、CD4+T细胞对反应性T细胞增殖的抑制作用减弱或消失。抑制功能受损并非由于反应性细胞耐药（通过与健康对照者的T细胞进行交叉实验表明）或调节性T细胞存活改变所致。
这些数据表明，缓解期WG患者中调节性T细胞比例增加但功能存在缺陷。这一观察结果可能与这种自身免疫性血管炎的发生和复发过程有关。
