Effect of glatiramer acetate (Copaxone) on CD4+CD25high3 T regulatory cells and their IL-10 production in multiple sclerosis
Effect of glatiramer acetate (Copaxone) on CD4+CD25high3 T regulatory cells and their IL-10 production in multiple sclerosis
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DOI：
10.1016/j.jneuroim.2003.08.001
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发表时间：
2003-11-01
影响因子：
3.3
通讯作者：
Huang, YM
中科院分区：
文献类型：
--
作者：
Putheti, P;Soderstrom, M;Huang, YM
CD 4（+）CD 25（高）T调节（Tr）细胞代表高IL-2受体α链表达细胞，已显示抑制CD 4（+）T细胞的增殖和细胞因子分泌，所述CD 4（+）T细胞被认为代表自身攻击性免疫中的重要效应细胞。因此，Tr细胞可能被认为在多发性硬化症（MS）的发病机制中具有重要意义。醋酸格拉替雷（GA;本研究的目的是检查GA对来自MS患者和健康对照（HQ.采用三色流式细胞术研究GA和致脑炎髓鞘碱性蛋白（MBP）肽83-89作为对照对血Tr细胞比例及其功能重要的细胞表面分子CD 45 RO、CD 69、CD 95和HLA-DR以及细胞内CTLA-4和IL-10的体外影响。与暴露于GA或MBP（83-99）无关，与三个治疗的MS患者组相比，在未治疗的MS患者和HC中表达HLA-DR的血液Tr细胞的水平保持较低。体外暴露于GA导致所有MS患者组中产生IL-10的Tr细胞水平升高，无论是否接受治疗以及HC。暴露于GA或MBP（83-99）对表达其他上述分子的Tr细胞的水平没有影响。我们得出结论，GA诱导Tr细胞产生升高的IL-10，其是均匀的并且独立于用IFN-β或GA或IFN-β +GA进行的MS处理。(C)2003 Elsevier B.V保留所有权利。
CD4(+)CD25(high) T regulatory (Tr) cells, representing high IL-2 receptor alpha chain expressing cells, have been shown to inhibit proliferation and cytokine secretion by CD4(+) T cells that are assumed to represent important effector cells in auto-aggressive immunity. Tr cells may therefore be considered of importance in the pathogenesis of multiple sclerosis (MS). Glatiramer acetate (GA; Copaxone) is approved as a disease-modulating agent that ameliorates the course of MS. The goal of this study was to examine in vitro effects of GA on Tr cells from MS patients subgrouped according to treatment without or with disease-modulating drugs, and healthy controls (HQ. Three-colour flow cytometry was used to investigate in vitro influence of GA, and of the encephalitogenic myelin basic protein (MBP) peptide 83-89 as control, on the blood Tr cell proportion and on their functionally important cell surface molecules CD45RO, CD69, CD95 and HLA-DR, and on intracellular CTLA-4 and IL-10. Irrespective of exposure to GA or MBP(83-99), levels of blood Tr cells expressing HLA-DR remained low in untreated MS patients and HC compared to the three treated MS patient groups. In vitro exposure to GA resulted in elevated levels of IL-10 producing Tr cells in all MS patient groups irrespective of receiving treatment as well as in HC. Exposure to GA or MBP(83-99) had no effects on levels of Tr cells expressing other above-mentioned molecules. We conclude that GA induces elevated IL-10 production by Tr cells that is uniform and independent of ongoing MS treatment with IFN-beta or GA or IFN-beta+GA. (C) 2003 Elsevier B.V All rights reserved.