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目的 :研究用扩散性抗原决定簇特异性Th2 /Tr1细胞被动免疫治疗实验性变态反应性脑脊髓炎 (EAE)的有效性和可能性。方法 :应用髓鞘蛋白脂质蛋白 (PLP) 139 15 1诱发EAE小鼠模型 ,通过转染方式建立具有高效表达IL 10特性的抗原特异性Th2 /Tr1样T细胞系 ,在EAE小鼠发病 6d后给予静脉注射。小鼠每天称体重并进行神经功能评分。实验结束时 ,取脊髓进行PLP免疫组化染色 ,应用数字化图像分析技术进行图像分析。结果 :注射扩散性抗原决定簇MBP87 99特异性Th2 /Tr1样T细胞的治疗组小鼠的临床评分明显改善 ,并伴有复发率的下降、首次复发时间的延迟 (P <0 0 5 )。PLP免疫组化染色的图像分析结果显示 ,接受MBP87 99特异性Th2 /Tr1样T细胞治疗组小鼠脊髓内PLP像素水平为正常值的 94 37%± 0 5 2 %,而对照组小鼠为正常PLP水平的 91 94%± 0 5 0 %(P <0 0 0 1) ,与对照组比较 ,治疗组小鼠脊髓内脱髓鞘病变下降 30 %。结论 :扩散性抗原决定簇特异性Th2 /Tr1细胞被动免疫治疗可明显减少脱髓鞘病变 ,改善EAE的临床症状 ,为多发性硬化的免疫治疗提供了理论依据。
Objective: To investigate the efficacy and feasibility of passive immunotherapy of experimental allergic encephalomyelitis (EAE) with diffusible antigenic determinant specific Th2 / Tr1 cells. Methods: The EAE mouse model was induced by myelin protein-lipoprotein (PLP) 139 15 1, and the antigen-specific Th2 / Tr1-like T cell line with high IL10 expression was established by transfection. After given intravenous injection. Mice were weighed daily and scored for neurological function. At the end of the experiment, the spinal cord was taken for PLP immunohistochemical staining and image analysis was performed using digital image analysis technique. Results: The clinical scores of mice treated with diffusible antigenic determinant MBP8799-specific Th2 / Tr1-like T cells were significantly improved with the relapse rate decreased and the time to initial relapse delayed (P <0.05). The results of PLP immunohistochemical staining showed that the PLP level in the spinal cord of mice receiving MBP8799-specific Th2 / Tr1-like T cells was 94 37% ± 0 5 2% of the normal value, while the control mice were The normal level of PLP was 91 94% ± 0 50% (P <0.01 01). Compared with the control group, the number of spinal cord demyelinating lesions in the treatment group decreased by 30%. Conclusion: Passive immunotherapy with diffuse antigen-specific Th2 / Tr1 cells can significantly reduce demyelinating lesions and improve the clinical symptoms of EAE, providing a theoretical basis for immunotherapy of multiple sclerosis.