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目的观察ICOSL敲基因(ICOSL knockout,ICOSL-KO)小鼠感染日本血吸虫后的免疫应答及其免疫病理反应。方法建立ICOSL-KO小鼠及野生型C57BL/6J小鼠日本血吸虫病模型,收集感染前(0周)和感染后(4～20周)的小鼠脾淋巴细胞用SEA进行诱导培养72小时后,采用ELISA双抗夹心法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-10、IL-13)细胞因子表达水平。应用ELISA法检测同期血清中SEA特异性抗体IgG、及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变。结果ICOSL-KO小鼠Th1细胞因子IFN-γ、IL-12表达明显高于野生型小鼠,而其Th2型细胞因子(IL-4、IL-10、IL-13)表达水平却显著低于野生型小鼠。ICOSL-KO小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著低于野生型C57BL/6J小鼠的水平,其Th2分化指数与IgG1/IgG2a的比值亦低于野生型小鼠的水平,特别是在感染7、12、16周后具有显著性差异。且ICOSL-KO小鼠的肝脏虫卵肉芽肿病变显著小于野生型小鼠。结论感染日本血吸虫的ICOSL-KO小鼠Th2免疫应答显著下调并导致肝虫卵肉芽肿病变减弱,表明ICOS–ICOSL信号通路在血吸虫病免疫病理中具有重要作用。
Objective To observe the immune response and immunopathological response of ICOSL knockout (ICOSL-KO) mice infected with Schistosoma japonicum. Methods ICOSL-KO mice and wild-type C57BL / 6J mice were established with schistosomiasis japonica. Splenic lymphocytes of mice before infection (0 weeks) and after infection (4 ~ 20 weeks) were collected and cultured for 72 hours by SEA. The expression of Th1 (IFN-γ, IL-12) and Th2 (IL-4, IL-10 and IL-13) in cultured supernatant was detected by ELISA. Serum levels of SEA-specific IgG and its subclasses IgG1 and IgG2a were detected by ELISA. HE staining was used to observe the pathological changes of mouse liver granuloma. Results The expression of Th1 cytokines IFN-γ and IL-12 in ICOSL-KO mice was significantly higher than that in wild-type mice, but the levels of Th2 cytokines (IL-4, IL-10 and IL-13) Wild-type mice. The serum levels of SEA-specific IgG and its subclasses IgG1 and IgG2a in ICOSL-KO mice were significantly lower than those in wild-type C57BL / 6J mice, and the ratio of Th2 differentiation index to IgG1 / IgG2a was also lower than that of wild-type mice Especially at 7, 12 and 16 weeks after infection. And ICOSL-KO mice liver granuloma lesions significantly smaller than wild-type mice. Conclusions The Th2 immune response of ICOSL-KO mice infected with Schistosoma japonicum is significantly down-regulated and the lesions of hepatic worm egg granulomas are attenuated. It indicates that ICOS-ICOSL signaling pathway plays an important role in the immunopathology of schistosomiasis.