FasL诱导EAE小鼠淋巴细胞凋亡的实验研究

Experimental Study on the FasL-Induced Apoptosis of Lymphocytes in Mouse Experimental Autoimmune Encephalomyelitis

为了解FasL在诱导EAE淋巴细胞凋亡中发挥的作用 ,我们用髓鞘碱性蛋白 (MBP )致敏小鼠 ,建立动物模型 实验性自身免疫性脑脊髓膜炎 (EAE )。分析了EAE动物淋巴细胞膜上Fas及FasL分子的表达水平 ,检测了分泌的细胞因子 ;用FasL分子诱导了EAE淋巴细胞凋亡。结果表明 ,应用MBP致敏KM小鼠 ,成功地建立了EAE模型 ,KM小鼠的发病率为6 8 3% ,发病程度为 1～ 2分 ;小鼠特异性淋转比对照组高 ,并与发病评分成正比 ;细胞因子分泌水平提示以Th2为主 ;EAE淋巴细胞Fas和FasL的表达及凋亡显著高于对照组 ;FasL诱导淋巴细胞凋亡剂量依赖曲线表明 ,在一个较小的浓度范围内呈现正相关 ,若加入单抗可部分阻断FasL诱导的凋亡。结果提示Fas FasL在EAE动物淋巴细胞凋亡中起了重要作用。

In order to evaluate the importance of FasL in the apoptosis of lymphocytes in experimental autoimmune encephalomyelitis (EAE),a mouse model of multple selerosis (MS) EAE (MS-EAE) that was induced by inoculation with myelin basic protein (MBP) and complete Freund's adjuvant into mice was constructed in this study,and the expressions of Fas and FasL on the surface of lymphocytes in EAE were analyzed thereby. It was found that the expressions of Fas and FasL as well as that of IL-4 and IL-10 of the lymphocytes in EAE were to be higher than that of the controls,and FasL could induce apoptosis of lymphocytes in a dose-dependent manner on the dosage of 1～100 ng/ml. The Fas-induced apoptosis could be blocked partially by the addition of specific monoclonal antibody against FasL. These results indicate that Fas-FasL interaction plays an important role in the pathogenesis of autoimmune disease.