日本血吸虫感染小鼠CD8+T细胞亚群的变化及其与肝脏免疫病理的相关性研究
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国家自然科学基金(81430052,81271861)


The association between CD8+ T cell subsets and immunopathology during Schistosoma japonicum infection
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    摘要:

    目的:研究CD8+T细胞中Tc1(CD3+CD8+ IFN-γ+)-Tc2(CD3+CD8+IL-4+)和调节性CD8+T细胞(CD8+CD28-)亚群在日本血吸虫感染导致的小鼠肝脏免疫病理发生发展中可能的作用。方法:取正常小鼠及日本血吸虫感染8周的小鼠脾脏淋巴细胞,采用流式细胞术检测Tc1-Tc2和调节性CD8+T细胞亚群分别占T淋巴细胞的比例及绝对数量,并分析感染血吸虫不同时期的CD8+T细胞亚群与血吸虫感染小鼠肝脏肉芽肿和肝纤维化指标的关系。结果:与正常对照小鼠比较,日本血吸虫感染后小鼠脾脏的单个核细胞绝对数显著增加(P < 0.001);日本血吸虫感染小鼠脾细胞中T细胞(CD3+)和CD8+T细胞(CD3+CD8+)的比例及绝对数均显著增加(P均 < 0.05);此外,感染小鼠脾淋巴细胞中Tc1-Tc2-调节性CD8+T比例均显著增加(P均 < 0.001);与正常小鼠相比,感染小鼠Tc2/Tc1比率显著增加(P < 0.001)。此外,多元线性逐步回归分析显示Tc2和调节性CD8+T细胞是影响血吸虫感染所致肝脏免疫病理的主要影响因素。结论:CD8+T细胞及其Tc1-Tc2-调节性CD8+T细胞亚群在日本血吸虫感染宿主的肝脏肉芽肿和纤维化发生发展中可能发挥重要作用。其中,Tc2和调节性CD8+T细胞可能分别促进/抑制血吸虫感染所致的肝脏免疫病理。

    Abstract:

    Objective:To study the role of CD8+T cell subsets in the development of liver immunopathology after Schistosoma japonicum (S japonicum)infection. Methods:Splenocytes were prepared from spleens of mice with S. japonicum infection at 0 and 8 weeks,and the proportions of Tc1,Tc2 and CD8+T regulatory cells in T cells were determined by FACS. The relationship between CD8+T cell subsets and liver immunopathology were analyzed. Results:Compared to the control group,the spleen mononuclear cells (MNC)in S. japonicum infected mice were increased significantly (P < 0.001). In addition,the proportions and the absolute numbers of T cells and CD8+T cells in spleen of S. japonicum infected mice were significantly increased(all P < 0.05). Furthermore,the proportions of Tc1,Tc2 and CD8+T regulatory cells were significantly increased at 8 weeks post-infection(all P values < 0.05)and the proportions of Tc2 cells increased more significantly than Tc1 cells. Multiple linear regression analysis showed that Tc2 and regulatory CD8+T cells were the main factors affecting liver immunopathology during S. japonicum infection. Conclusion:Tc1,Tc2 and CD8+ T regulatory cells in splenocytes increased significantly after S. japonicum infection. Tc2 and regulatory CD8+ T cells play critical roles in promoting and inhibiting the liver immunopathology,respectively.

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俞 敏,陈梦星,徐志鹏,许 磊,陈晓军,周 莎,朱继峰,李 薇,金 鑫,宋 娴,李亚琳,张 阳,刘 丰,苏 川.日本血吸虫感染小鼠CD8+T细胞亚群的变化及其与肝脏免疫病理的相关性研究[J].南京医科大学学报(自然科学版),2015,(11):1497-1503

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  • 收稿日期:2015-06-17
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  • 在线发布日期: 2015-11-30
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