Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS

被引:65
作者
Chen, M
Gran, B
Costello, K
Johnson, K
Martin, R
Dhib-Jalbut, S
机构
[1] Univ Maryland, Sch Med, Baltimore, MD 21201 USA
[2] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA
[3] Baltimore VA Med Ctr, Baltimore, MD 21201 USA
来源
MULTIPLE SCLEROSIS | 2001年 / 7卷 / 04期
关键词
multiple sclerosis; glatiramer acetate; Copaxone((R)); Copolymer-1; immune deviation;
D O I
10.1177/135245850100700401
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:209 / 219
页数:11
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