共刺激分子B7-1介导Th1/Th2免疫应答对日本血吸虫虫卵肉芽肿病变的影响

目的观察B7-1激发型mAb的体内注射对日本血吸虫感染小鼠Th1/Th2免疫偏移的影响及对虫卵肉芽肿病变的调节作用,探讨干预共刺激信号调控Th1/Th2免疫偏移控制血吸虫虫卵肉芽肿病变的新途径。方法小鼠感染日本血吸虫尾蚴后4w给予腹腔内注射B7-1激发型mAb,于6、8wk摘眼球取血收集血清,用ELISA双抗体夹心法测定血清中抗体IgGI、gG1I、gG2a的水平;同时取脾淋巴细胞培养72h,同法测定培养上清中细胞因子IFN-γ和IL-4的表达水平;并且检测感染小鼠虫卵肉芽肿体积。结果B7-1激发型mAb能显著下调感染小鼠血清IgG水平,并能显著上调IFN-γ的表达水平,下调IL-4的表达水平,同时能使虫卵肉芽肿体积显著减小。反映Th1/Th2免疫偏移的IgG1/IgG2a有下降趋势。结论B7-1激发型mAb能调节Th1/Th2免疫应答,诱导免疫反应向Th1方向偏移,从而为控制日本血吸虫虫卵肉芽肿病变的免疫治疗新途径提供了实验依据。

Influence of the co-stimulatory factor B7-1-mediated Th1/Th2 response on the granulomatous lesions induced by eggs of Schistsoma japonicum

In order to observe the effect of injection with B7-1 active monoclonal antibody on the Th1/Th2 deviation and the regulation of the granulomatous lesions induced by eggs of Schistosoma japonicum and to probe a new way to control the granuloma formation through the interference with the co-stimulatory signaling pathway,mice infected with cercariae of S.japonicum were administrated intra-peritoneally with B7-1 active mAb 4 weeks after infection,and the spleen lymphocytes of the inoculated mice were obtained.Six to eight weeks after infection,sera of mice were to be taken and the levels of serum antibodies IgG,IgG1 and IgG2a were detected by the double antibody sandwich ELISA,and the expression levels of cytokines IFN-γ and IL-4 in the supernatants of spleen cells cultivated for 72 hrs.Meanwhile,the size of granuloma induced by eggs of worms in the infected mice was measured.The experimental results showed that the B7-1 active mAb could inhibit markedly the level of IgG,but partially inhibit those of IgG1 and IgG2a.However,a pronounced up-regulation of the expression level of IFN-γ with a simultaneous down-regulation of the expression level of IL-4 could be demonstrated 6 weeks after treatment with the B7-1 active mAb.In addition,the size of granuloma induced by eggs of worms was markedly decreased in mice treated with mAb.It suggests that co-stimulatory factor B7-1 active monoclonal antibody could mediate the Th1/Th2 response to the Th1 deviation,so as to control the granuloma formation induced by eggs of S.japonicum..