Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
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DOI：
10.1172/jci8970
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发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Hafler, DA
中科院分区：
文献类型：
--
作者：
Duda, PW;Schmied, MC;Hafler, DA
我们研究了醋酸格拉替默（丙氨酸、赖氨酸、谷氨酸和酪氨酸的随机共聚物）对多发性硬化症（MS）患者抗原特异性t细胞反应的影响。醋酸格拉替雷默（Copaxone）：在MS或健康受试者制备的t细胞系中，作为一种通用抗原，诱导增殖，不依赖于任何先前的聚合物暴露。然而，对于大多数患者来说，每日注射醋酸格拉替默可消除这种t细胞反应，并促进Th2细胞特征IL-5和IL-13的分泌。存活的醋酸格拉替默反应性T细胞表现出更大程度的退化，通过对组合肽库的交叉反应反应来测量。因此，在某些个体中，体内给药醋酸格拉替默诱导分泌Th2细胞因子的高度交叉反应的T细胞。据我们所知，醋酸格拉替默是第一种抑制人类自身免疫性疾病并通过参与t细胞受体改变免疫功能的药物。该化合物可用于多种自身免疫性疾病，其中免疫偏离到Th2型反应是可取的。
We examined the effect of glatiramer acetate, a random copolymer of alanine, lysine, glutamic acid, and tyrosine, on antigen-specific T-cell responses in patients with multiple sclerosis (MS). Glatiramer acetate (Copaxone) Functioned as a universal antigen, inducing proliferation, independent of any prior exposure to the polymer, in T-cell Lines prepared from MS or healthy subjects. However, for most patients, daily injections of glatiramer acetate abolished this T-cell response and promoted the secretion of IL-5 and IL-13, which are characteristic of Th2 cells. The surviving glatiramer acetate-reactive T cells exhibited a greater degree of degeneracy as measured by cross-reactive responses to combinatorial peptide libraries. Thus, it appears that, in some individuals, in vivo administration of glatiramer acetate induces highly cross-reactive T cells that secrete Th2 cytokines. To our knowledge, glatiramer acetate is the first agent that suppresses human autoimmune disease and alters immune function by engaging the T-cell receptor. This compound may be useful in a variety of autoimmune disorders in which immune deviation to a Th2 type of response is desirable.