日本血吸虫感染小鼠调节性T细胞水平动态变化及功能逆转研究  

Dynamics of CD4^+CD25^+ regulatory T cells of mice infected with Schistosoma japonicum and reversal of function

作　　者：余传信[1] 吴宇迪[1] 王玠[1] 殷旭仁[1] 华万全[1] 钱春艳[1] 梁幼生[1] 高琪[1] 

机构地区：[1]江苏省血吸虫病防治研究所,卫生部寄生虫病预防与控制技术重点实验室,江苏省寄生虫分子生物学重点实验室,江苏省寄生虫病重点学科,江苏无锡214064

出　　处：《中国病原生物学杂志》2009年第10期754-757,776,共5页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.30671833,30471515);国家十一五重大专项(No.2008ZX10004-011);江苏省自然科学基金项目(No.BK2008110);江苏省科技厅公益专项基金项目(No.BM2007704);江苏省医学重点人才基金项目(No.RC2007095)

摘　　要：目的观察日本血吸虫感染小鼠调节性T细胞水平动态变化,筛选调节性T细胞功能抑制因子。方法以日本血吸虫尾蚴感染小鼠,采用流式细胞分析法检测不同感染阶段小鼠体内调节性T细胞水平;通过检测小鼠血清中细胞因子的水平变化,观察免疫反应的极化过程;采用磁珠分离法纯化小鼠脾脏的调节性T细胞,人工设计合成2条寡核苷酸(CpG1-ODN,CpG2-ODN),通过淋巴细胞增殖试验筛选能逆转调节性T细胞功能的刺激因子。结果流式细胞分析发现,随着血吸虫感染进程的发展,小鼠外周血及脾脏调节性T细胞水平逐渐增加,免疫反应逐步向Th2型极化,血清IL-5水平增加,IFN-γ下降。淋巴细胞增殖试验显示,人工合成的寡核苷酸(CpG2-ODN)能有效刺激淋巴细胞增殖,使淋巴细胞的IL-2分泌增加,TGF-γ下降,并能解除调节性T细胞对效应T细胞增殖的免疫抑制作用。结论血吸虫感染可增加小鼠体内调节性T细胞水平,诱导免疫反应向Th2型极化。寡聚核苷酸CpG2-ODN能逆转调节性T细胞的免疫抑制功能。Objective To investigate the dynamics of CD4^＋ CD25^＋ regulatory T cells of mice infected with Schistosoma japonicurn and ascertain factors that could reverse the inhibition of CD4^＋ CD25^＋ regulatory T cells. Methods Mice were infected with cercaria of S. japonicum and the dynamics of CD4^＋ CD25^＋ regulatory T cells of these mice were examined in different stages of infection using a fluorescence-activated cell sorter （FACS） ; the polarization of the immune response was monitored by measuring serum cytokines using enzyme-linked immunosorbent assay （ELISA）. The spleen CD4^＋ CD25^＋ regulatory T cells of infected mice were isolated with a magnetic mierobead system. Two oligo-nueleotide fragments （CpG1-ODN, CpG2-ODN） were synthesized, and a lymphocyte proliferation test was used to screen for those that reversed the inhibition of CD4^＋ CD25^＋ regulatory T cells. Results The data on FACS of CD4^＋ CD25^＋ regulatory T cells in different stages of infection showed that the levels of CD4^＋ CD25^＋ regulatory T cells in peripheral blood and the spleens of mice increased gradually as the schistosome infection developed. The immune response of mice was Th2-polarized with elevated serum IL-5 and decreased IFN-γ. CpG2-ODN stimulated the lymphoeytes to proliferate effectively and reversed the immunosuppressive action of CD4^＋ CD25^＋ regulatory T cells in a lymphocyte proliferation test. Conclusion When mice were infected with S. japonicum, the levels of CD4^＋ CD25^＋ T regulatory cells in peripheral blood and the spleen increased gradually and immune response was Th2-polarized. CpG2-ODN reversed the immunosupression of CD4^＋ CD25^＋ T regulatory cells.

关 键 词：血吸虫 日本 感染 调节性T细胞 寡聚核苷酸(CpG-ODN) 逆转 

分 类 号：R383.24[医药卫生—医学寄生虫学]