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/jci200214380
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发表时间：
2002-03-01
影响因子：
15.9
通讯作者：
Racke, MK
中科院分区：
文献类型：
--
作者：
Karandikar, NJ;Crawford, MP;Racke, MK
醋酸格拉替雷（GA；Copaxone）是一种谷氨酸、赖氨酸、丙氨酸和酪氨酸的随机共聚物，用于治疗多发性硬化症 (MS) 患者。为了研究药物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 细胞反应的精确性质。我们在此证明，健康个体和未经治疗的多发性硬化症患者对 GA 表现出显着的 T 细胞增殖反应。然而，这些反应在不同的 T 细胞亚群中是不同的。虽然 GA 诱导的 CD4(+) T 细胞反应在健康个体和 MS 患者中相当，但 CD8(+) T 细胞反应在未经治疗的 MS 患者中明显较低。 GA 治疗导致这些 CD8(+) 反应上调，并恢复到健康个体中观察到的水平。 CD4(+) 和 CD8(+) GA 特异性反应均受 HLA 限制。 GA 治疗还诱导 GA 特异性 CD4(+) 和 CD8(+) T 细胞的细胞因子谱发生变化。据我们所知，这项研究首次提供了 GA 特异性 CD8(+) T 细胞反应及其在治疗过程中上调的直接免疫表型证据，这可能表明这些反应在药物的免疫调节作用中发挥作用。
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.