Glatiramer acetate-reactive peripheral blood mononuclear cells respond to multiple myelin antigens with a Th2-biased phenotype
Glatiramer acetate-reactive peripheral blood mononuclear cells respond to multiple myelin antigens with a Th2-biased phenotype
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DOI：
10.1016/s0165-5728(03)00170-x
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发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Martin, R
中科院分区：
文献类型：
--
作者：
Dhib-Jalbut, S;Chen, M;Martin, R
醋酸格拉替雷（GA）在多发性硬化（MS）中的一种有利的作用机制涉及GA反应性Th 2细胞的诱导，据信所述GA反应性Th 2细胞进入中枢神经系统并介导响应于交叉反应性髓鞘抗原的旁观者抑制。为了检验这一假设，我们研究了增殖反应和细胞因子释放从外周血单核细胞（PBMC）的12 p MS患者治疗GA，在响应16髓鞘肽，以前被描述为免疫显性或致脑炎和破伤风肽作为对照抗原。通过酶联免疫吸附测定（ELISA）测定干扰素-γ（IFN-γ）和IL-5（分别为Th 1和Th 2应答的标志物）。来自12名患者中的9名（75%）的GA刺激的PBMC增殖为一种或多种髓鞘肽。阴离子在测试的16种肽中，来自大多数患者的GA刺激的PBMC响应于MOG而增殖（21-44）。三分之二患者的PBMCs响应髓鞘肽而产生IL-5，而其中一半产生IFN-γ。Th 1/Th 0/Th 2细胞因子表型表明，从12例患者中的10例的反应是Th 0或Th 2偏向。两名患者的反应，p为Th 1偏倚。相反，一些髓磷脂特异性T细胞系（TCL）通过增殖（21个TCL中的3个）、IL-5释放（21个TCL中的11个）和IFN-γ释放（21个TCL中的3个）来响应GA。这些结果表明GA反应性TCLs可以以Th 2偏向的方式对髓磷脂肽的谱做出响应，这与旁观者抑制的概念一致。此外，一些髓鞘特异性TCLs能够识别GA。倾向于产生比IFN-γ更多的IL-5，这表明药物具有全身调节作用。(C)2003 Elsevier B. V.保留所有权利。
One favored mechanism of action of glatiramer acetate (GA) in multiple sclerosis (MS) involves the induction of GA-reactive Th2 cells that are believed to enter the central nervous system and mediate bystander suppression in response to cross-reactive myelin antigens. To test this hypothesis, we examined the proliferative response and cytokine release from peripheral blood mononuclear cells (PBMCs) of 12 p MS patients treated with GA, in response to 16 myelin peptides that were previously described as immunodominant or encephalitogenic and a tetanus peptide as a control antigen. lnterferon-gamma (IFN-gamma) and IL-5 (markers of Th1 and Th2 responses, respectively) were assayed by enzyme-linked immunosorbent assay (ELISA). GA-stimulated PBMCs from 9 of 12 patients (75%) proliferated to one or more myelin peptides. Anions! the 16 peptides tested, GA-stimulated PBMCs from the majority of the patients proliferated in response to MOG(21-44). PBMCs from two thirds of the patients produced IL-5 in response to myelin peptides, while half of them produced IFN-gamma. Th1/Th0/Th2 cytokine phenotypes demonstrated that responses from 10 of 12 patients were either Th0- or Th2-biased. Responses from two patients, p were Th1-biased. Conversely, some myelin-specific T-cell lines (TCLs) responded to GA by proliferation (3 of 21 TCLs), IL-5 release (11 of 21 TCLs), and IFN-gamma release (3 of 21 TCLs). These results indicate that GA-reactive TCLs can respond to a spectrum of myelin peptides in a Th2-biased fashion, which is consistent with the concept of bystander suppression. Furthermore, some myelin-specific TCLs are able to recognize GA. with a tendency to produce more IL-5 than IFN-gamma, which would suggest a systemic modulatory effect of the drug. (C) 2003 Elsevier B.V. All rights reserved.