日本血吸虫慢性感染致CD_4^+ T细胞凋亡的分子基础

Molecular basis for the apoptosis of CD_4^+ T cells induced by chronic infection of Schistosoma japonicum

目的 立足于全基因水平考察日本血吸虫慢性感染小鼠CD+4T细胞的凋亡相关基因的变化。方法 采用三色流式细胞术结合高密度寡核苷酸芯片 (Affemetrix芯片 ) ,对日本血吸虫感染 13周的小鼠脾脏中的CD+4T细胞进行凋亡观察及基因转录分析 ,获得凋亡相关基因的表达图谱。结果 日本血吸虫慢性感染小鼠CD+4T细胞的凋亡率均明显高于正常小鼠 (P <0 0 1) ;感染小鼠的CD+4T细胞中有 2 5个凋亡相关基因与正常小鼠相比有显著性差异 ,包括凋亡促进基因—生长抑制和DNA损伤 -GADD家族和肿瘤坏死因子α诱导蛋白 3,凋亡抑制基因—IAP等。结论 日本血吸虫慢性感染小鼠CD+4T细胞的凋亡可能是导致宿主免疫下调的原因之一。凋亡通路中存在复杂的凋亡促进基因和抑制基因的相互作用 ,其中肿瘤坏死因子α诱导蛋白 3可能是日本血吸虫感染诱导CD+4T细胞凋亡的特征性因子。

The changes of expression of apoptosis associated genes on CD + 4T cells of mice chronically infected with Schistosoma japonicum were investigate on the genomic scale in the present study.The apoptotic splenic CD + 4T cells of mice infected with S japonicum 13 weeks before were examined by three color flow cytometery with AnnexinV/P1 staining, and the cDNA microarray technique was used to explore the expression profile of the apoptosis associated genes.It was found that the rate of apoptotic CD + 4T cells in the infected mice was significantly higher than that of normal mice,in which there were 25 apoptosis associated genes showing significant changes,including apoptosis promoting gene growth inhibition and DNA damage GADD family,tumor necrosis factor αinduced protein 3 and apoptosis inhibitory gene IAP.It concludes that apoptosis of CD + 4 T cells induced by chronic infection of S.japonicum might be the cause for the down modulation of immune responses in this chronic infection.The interaction of the apoptotic genes and the apoptosis inhibitory genes constitutes the complicated networks regulating the apoptosis of CD + 4T cells,in which tumor necrosis factor αinduced protein 3 may play an important role.