Tim-2在日本血吸虫感染小鼠Th2优势应答中的作用

The role of Tim-2 in Th2-biased response in mice with Schistosoma japonicum infection

目的观察日本血吸虫感染小鼠T细胞免疫球蛋白黏蛋白分子-2(Tim-2)基因表达与干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)水平的动态变化,探讨Tim-2在血吸虫感染小鼠Th1/Th2免疫平衡中的可能机制。方法以日本血吸虫尾蚴感染小鼠,采用RT-PCR、ELISA法检测不同感染阶段小鼠脾淋巴细胞中Tim-2和IFN-γ、IL-4水平;HE染色观察组织学改变;免疫组化法检测Tim-2在肝脏虫卵肉芽肿中的表达。结果日本血吸虫尾蚴感染后3周小鼠脾淋巴细胞IFN-γmRNA及其培养上清中蛋白表达水平均显著增高(P<0.01);而IL-4 mRNA及其培养上清中蛋白表达水平于感染6周、9周显著增高(P<0.01);HE染色显示随着血吸虫感染进程的发展,肝脏肉芽肿面积逐步增大,6周达峰值,随后有所下降;RT-PCR结果显示尾蚴感染6周的小鼠脾细胞中Tim-2基因表达较正常对照组显著增高;免疫组化法分析显示,小鼠肝脏虫卵肉芽肿Tim-2表达主要分布在虫卵及其周围。结论慢性血吸虫感染可诱导宿主全身性的Th2优势应答,Tim-2可能参与慢性感染宿主机体Th1/Th2免疫平衡的调节。

Objective To explore the role of T cell immunoglobulin domain and mucin domain （Tim-2） family in Th2-biased immune response in mice infected with Schistosoma japonicum, and the possible mechanism by which a balanced Thl/Th2 immunity evoked in the infected hosts is discussed. Methods Mice were infected with cercaria of S. japonicum and the dynamics of Tim-2 and IFN-γ, IL-4 expression in the spleen lymphocytes on different sta- ges of S. japonicum infected mice were examined using RT-PCR or ELISA. The histological analysis was performed by HE staining, and the Tim-2 expressions in the hepatic granuloma were measured by immunohistochemisty exami- nation. Results The levels of IFN-γ mRNA in the spleen lymphocytes and the supernatants of spleen lymphocytes were elevated significantly after 3 weeks of schistsome infection in mice（P 〈 0. 01 ）, while those of IL-4 enhanced on 6 and 9 weeks post-infection compared with the control mice （P 〈 0.01 ）. Tim-2 mRNAs were elevated in the spleen lymphocytes of 6 weeks infection mice. HE staining showed that the size of granuloma reached its maximum at 6 weeks after infection, and shrinked with hepatic fibrosis formation 12 weeks post-infection. Immunohistochemi- cal observation demonstrated that Tim-2 proteins were closely associated with the eggs in the hepatic granuloma. Conclusion Chronic S. japonicun infection can evoke Th2-biased response systemically. Tim-2 expressed on Th2 cells may act as a down-regulated molecule to maintain the balanced of Thl/Th2 immunity in the hosts.