慢性实验性变态反应性脑脊髓炎小鼠模型不同阶段抗原提呈细胞免疫应答作用分析

The study of immune response of APC in different stage of Chronic EAE

目的对MOG35-55肽段诱导的实验性变态反应性脑脊髓炎(EAE)小鼠不同时期病理变化特点进行观察分析,探讨在EAE的发生、发展和迁延过程中抗原提呈细胞(APC)所起的作用及其作用机制。方法利用MOG35-55肽段作为免疫原诱导C57BL/6小鼠制作慢性非缓解型EAE模型,在不同时期观察实验动物神经功能变化,进行组织病理学检查,通过WB、RT-PCR等方法检测部分免疫指标。结果研究发现MOG35-55肽段可以成功诱导出慢性非缓解型EAE动物模型。与对照组比较,EAE组小鼠在发病过程中,脑组织出现以单核巨噬细胞、淋巴细胞为主的浸润;脑组织中C3表达降低(P<0.05),MHCⅠ、MHCⅡ和IL-12蛋白表达增加(P<0.05);IL-27和B7 mRNA表达增加(P<0.05)。结论中枢神经系统内APC的活化、MHC分子、IL-12表达增加是EAE发生的早期事件并贯穿整个病理变化过程,由APC免疫应答引发的下游伴随事件可以造成EAE动物模型髓鞘直接损伤,APC可能是慢性EAE最终发生的最重要启动和致病因素之一。

Objective To analyze the pathological changes in different periods of MOG35 - 55 peptide - induced EAE mice, trying to in order to reveal the role and its mechanism of difference immune responses during the occurrence, development and persistent process of EAE. Method MOG35 - 55 peptide as an immunogen induced C57 BL/6 mice to produced chronic non - remitting EAE mod- el. We used the method of histopathological to observe the changes in neurological function at different times of experimental animals, at the same time, Western blot, and RT - PCR technologies were used to detect some important indicators of immune parameters and make a comprehensive analysis. Result The study found that MOG35 - 55 peptide can be successfully induced the chronic non - remitting EAE animal model. Compared with control group,lymphocyte and mononuclear macrophages of proliferation and infiltrating;The expression of C3 protein were decreased in brain （ P 〈 0.05 ）, the expressions of MHC I ,MHC U and IL - 12 protein were increased （ P 〈 0.05 ） ; the expressions of IL - 27 and B7 mRNA were increased （P 〈 0.05 ）. Conclusion The activation of the APC,increased expression of MHC molecule and IL - 12 in the central nervous system is an early event in EAE and throughout the entire process of its pathological changes. Downstream events caused by immune responses of the APC can cause EAE animal model myelin damage directly, the APC is probably the most important start and pathogenic factor for the chronic EAE happened eventually.