多发性硬化症患者APL特异性T细胞系免疫生物学特性分析

Study on the Characteristics of APL Specific T Cell Lines Generated from Patients with Multiple Sclerosis

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。

To assess the immune responses induced by altered peptide ligand (APL) in patients with multiple sclerosis (MS) who had recieved APL subcutaneously one year before in a phase I clinical trial (10 or 20mg,4 times per week),the frequency of APL reactive T cell line was determined after the second cycle of restimulation by using a split well microtitre culture technique,and the specificity of these T cell lines was analyzed by co cultivation of myelin basic protein (MBP) with MBP predominant peptide 83 99,and the cytokine profile was measured by ELISA Experimental results revealed that 31 APL T cell lines were generated from 5 MS patients treated with APL of which 23 were set up from 10 patients with other neurological diseases (OND) with a frequency of APL specific T cell line at 31 6%±23 7% in patients and 5%±2% in control group These APL specific T cell lines showed fine specificity to APL,and the cross reactions to MBP were 19 4%(6/31) in treated group and 4 3%(1/23) in control group respectively;no cross reaction with the MBP predominant peptide 83 99 was found In case of the APL specific T cell lines isolated from MS patients treated with APL,67% secreted IL 5 and IL 13,thus indicating that these cell lines showed the characteristics of the Th2 type cytokine profile These results suggested that this altered MBP peptide could be used as a therapeutic agent through their effect on up regulating the Th2 regulatory cells and by lessening the autoreactive T cell mediated immune demage reactions