Glatiramer acetate (Copaxone) therapy induces CD8(+) T cell responses in patients with multiple sclerosis.
Glatiramer acetate (Copaxone) therapy induces CD8(+) T cell responses in patients with multiple sclerosis.
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DOI：
10.1172/jci14380
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发表时间：
2002-03
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影响因子：
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通讯作者：
Nitin J. Karandikar;M. P. Crawford;Xiao-ying Yan;R. Ratts;J. Brenchley;D. Ambrozak;A. Lovett-racke;E. Frohman;P. Stastny;D. Douek;R. Koup;M. Racke
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作者：
Nitin J. Karandikar;M. P. Crawford;Xiao-ying Yan;R. Ratts;J. Brenchley;D. Ambrozak;A. Lovett-racke;E. Frohman;P. Stastny;D. Douek;R. Koup;M. Racke
醋酸格拉替雷（GA; Copaxone）是谷氨酸、赖氨酸、丙氨酸和酪氨酸的无规共聚物，用于治疗多发性硬化症（MS）患者。为了研究药物的免疫调节作用的机制，我们使用免疫表型方法来表征GA诱导的T细胞应答的确切性质。我们在这里证明，健康个体和未经治疗的MS患者表现出突出的T细胞增殖反应GA。然而，这些反应在不同的T细胞亚群中是不同的。尽管GA诱导的CD 4（+）T细胞应答在健康个体和MS患者中相当，但CD 8（+）T细胞应答在未经治疗的MS患者中显著较低。用GA治疗导致这些CD 8（+）应答上调，并恢复到在健康个体中观察到的水平。CD 4（+）和CD 8（+）GA特异性反应都是HLA限制性的。GA疗法还诱导GA特异性CD 4（+）和CD 8（+）T细胞的细胞因子谱的变化。据我们所知，这项研究提供了GA特异性CD 8（+）T细胞应答及其在治疗过程中上调的第一个直接免疫表型证据，这可能表明这些应答在药物的免疫调节作用中的作用。
Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine that is used therapeutically in patients with multiple sclerosis (MS). To investigate the mechanism of the drug's immunomodulatory effect, we used immunophenotypic approaches to characterize the precise nature of GA-induced T cell responses. We demonstrate here that healthy individuals and untreated MS patients exhibit prominent T cell proliferative responses to GA. However, these responses are different in distinct subsets of T cells. Whereas GA-induced CD4(+) T cell responses are comparable in healthy individuals and MS patients, CD8(+) T cell responses are significantly lower in untreated MS patients. Treatment with GA results in upregulation of these CD8(+) responses with restoration to levels observed in healthy individuals. Both CD4(+) and CD8(+) GA-specific responses are HLA-restricted. GA therapy also induces a change in the cytokine profile of GA-specific CD4(+) and CD8(+) T cells. This study provides the first direct immunophenotypic evidence, to our knowledge, of GA-specific CD8(+) T cell responses and their upregulation during the course of therapy, which may suggest a role for these responses in the immunomodulatory effects of the drug.