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本文报告采用髓鞘碱性蛋白 (MBP )的修饰性肽段配体 (APL )对多发性硬化症 (MS )患者治疗 1年后 ,在细胞克隆水平分析T细胞免疫应答的结果。从 5例患者外周血淋巴细胞中建立了 31个APL特异性T细胞系。首先测定患者和健康人体内APL特异性T细胞的反应频率 ,发现患者中平均为 31 6%± 2 3 7% ,而 10例对照者中仅为 5 %± 2 %。 31株APL反应性T细胞系对APL抗原表现出高度的增殖特异性。同时发现 ,APL特异性T细胞系与MBP优势肽段 (氨基酸 83 99)发生交叉反应的比例 ,患者中为 19 4% (6/ 31) ,而对照组中仅有 4 3% (1/ 2 3)。未发现与MBP优势肽段 83 99有交叉反应。来自MS治疗组的APL特异性T细胞系中 ,67%分泌IL 5和 /或IL 13,表明这些T细胞系具有Th2细胞特性。以上结果提示 ,这一修饰性MBP多肽作为一种治疗性疫苗 ,有可能在体内通过诱导Th2调节细胞 ,下调自身反应性T细胞介导的免疫损伤 ,发挥治疗作用。
This article reports the results of a T cell immune response at the level of cell clones after 1 year of treatment of patients with multiple sclerosis (MS) with a modified peptide ligand (APL) of myelin basic protein (MBP). Thirty-one APL-specific T cell lines were established from 5 patients with peripheral blood lymphocytes. The frequency of APL-specific T cells in patients and healthy individuals was determined first and found an average of 31 6% ± 2 37% in patients and only 5% ± 2% of 10 controls. Thirty APL-reactive T cell lines showed a high degree of proliferation specificity for APL antigens. Also, the percentage of APL-specific T cell lines that cross-reacted with the MBP-dominant peptide (amino acid 83 99) was 19.4% (6/31) in patients and only 43% (1/2) 3). No cross-reaction with the MBP dominant peptide 8399 was found. Of the APL-specific T cell lines from the MS treated group, 67% secreted IL5 and / or IL13, indicating that these T cell lines have Th2 cell properties. The above results suggest that this modified MBP polypeptide, as a therapeutic vaccine, may have a therapeutic effect in vivo by inducing Th2-regulated cells and downregulating autoreactive T cell-mediated immune damage.