Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS
Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS
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DOI：
10.1191/135245801680209303
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发表时间：
2001-08-01
期刊：
影响因子：
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通讯作者：
Dhib-Jalbut, S
中科院分区：
文献类型：
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作者：
Chen, M;Gran, B;Dhib-Jalbut, S
醋酸格拉替雷（GA）是一种获批的多发性硬化症（MS）治疗药物。所提出的作用机制是诱导以保护性抗炎Th 2应答为特征的GA特异性T细胞。我们在II型MS患者中测试了这一假设，患者接受GA治疗1 - 19个月。通过ELISA测定GA特异性T细胞系（TCL）上清液中的干扰素-γ和IL-5（分别为Th 1和Th 2应答的标志物）。根据IFN-γ/IL-5分泌的比率定义Th 1/Th 2偏倚。生成了58个治疗前和75个治疗中GA特异性TCL。GA-TCL中的治疗平均IL-5水平显著增加，而IFN-γ水平显著降低。因此，IFN γ/IL-5的比率也向有利于Th 2应答的方向移动。与治疗前相比，治疗期间分类为Th I的GA-TCL百分比降低，而分类为TH的百分比增加。在治疗期间产生的一些GA特异性TC（约25%）响应于MBP和免疫显性MBP肽83-99而主要分泌IL-5，表明这些交叉反应性抗原可以充当GA反应性TCL的部分激动剂。这些结果强烈表明，GA在MS中的作用机制涉及诱导具有主要Th 2细胞因子谱的交叉反应性GA特异性T细胞。
Glatiramer acetate (GA) is an approved treatment for multiple sclerosis (MS). The proposed mechanism of action is the induction of GA-specific T cells characterized by protective anti-inflammatory Th2 response. We tested this hypothesis in II MS patients treated with GA from 1 - 19 months. Interferon-gamma and IL-5 (markers of Th1 and Th2 responses respectively) were assayed by ELISA in GA-specific T-cell lines (TCL) supernatants. Th1/Th2 bias was defined based on the ratio of IFN-gamma /IL-5 secretion. Fifty-eight pre-treatment and 75 on-treatment GA-specific TCL were generated. On-treatment mean IL-5 levels in GA-TCL increased significantly, whereas those for IFN-gamma were markedly reduced. Consequently, the ratio of IFN gamma /IL-5 also shifted in favor of a Th2 response. The percentage of GA-TCL classified as Th I was decreased, whereas those classified as TH increased on-treatment as compared to pre-treatment. Some GA-specific TC (approximately 25%) generated during treatment secreted predominantly IL-5 in response to MBP and the immunodominant MBP peptide 83-99, indicating that these crossreactive antigens can act as partial agonists for GA-reactive TCL. These results strongly suggest that the mechanism of action of GA in MS involves the induction of crossreactive GA-specific T cells with a predominant Th2 cytokine profile.