基因表达谱芯片分析日本血吸虫感染慢性期CD4^+细胞的应答特征

Characteristic response of CD4^+ cell in chronic Schistosoma japonicum in fection by gene expression profiling

目的 立足于全基因水平考察日本血吸虫慢性感染小鼠CD4+细胞的相关细胞因子的变化 ,探讨其与疾病的相关性。方法 采用高密度寡核苷酸芯片 (Affemetrix芯片 )结合三色流式细胞术 ,对日本血吸虫感染 13周的小鼠脾脏中的CD4+细胞进行基因转录及蛋白表达水平的分析 ,获得相关细胞因子的变化图谱。结果 日本血吸虫慢性感染小鼠CD4+细胞中IL 4的转录及蛋白表达水平均明显高于正常小鼠 (P <0 .0 5) ,尤其以可溶性虫卵抗原刺激后最为显著 (P <0 .0 1) ;感染小鼠IFN γ的转录及蛋白表达水平也有所增高 ,但不及IL 4的升高程度 ;IL 10、IL 1β、小诱导细胞因子(smallinduciblecytokine)等因日本血吸虫的感染而升高 ,但TGF β1呈下降趋势。结论 日本血吸虫慢性感染小鼠细胞因子分泌谱表现为Th1和Th2型细胞因子并存的格局 ,但以Th2应答为主。

Objective The changes of cytokine expression on a genomic scale in CD4 + cell of mice c hronically infected with Schistosoma japonicum and their roles in the pathog enesis of schistosomiasis were studied. Methods CD4 + cells were isolated from sp le ens of mice 13 wk infected with Schistosoma japonicum. We used the cDNA micr oarr ay technique to explore the cytokine gene expression profile of CD4 + cells f ro m normal and chronic infected mice. Three-color flow cytometry was performed to study intracellular protein levels of IFN-γ、IL-4 of CD4 + cell. Results In the CD4 + cell of chronically infected mice, IL-4 was remarkably increase d at both transcription and protein expression levels (P<0.05), especially a fter stimulation with soluble egg antigen (P<0.01); IFN-γ was also upregul a ted, but not as high as IL-4; IL-10、IL-1β and small inducible cytokine so o n show higher transcription levels associated with Schistosoma japonicum inf ection; Howerver, TGF-β1 was downmodulated in infected mice. Conclusions Although both type-1 and type-2 cytokines can be produced in accordance with d istinct antigens in chronic infection of Schistosoma japonicum, type-2 resp onse is predominate. The cytokines and the chemokines induced may play important roles in the pathogenesis of schistosomiasis.