Co-signaling molecules are molecules whose ligands on the surface of cells interact with receptors on the surface of T cells to convey stimulatory or inhibitory signals to regulate immune responses.Co-signaling molecu...Co-signaling molecules are molecules whose ligands on the surface of cells interact with receptors on the surface of T cells to convey stimulatory or inhibitory signals to regulate immune responses.Co-signaling molecules play an important role in tumor and autoimmune diseases.Lately,studies have shown that co-signaling molecules are also involved in the regulation of maternal-fetal immune tolerance,and abnormalities of co-signaling molecules may lead to the imbalance of maternal-fetal immune tolerance,resulting in recurrent abortion,eclampsia and other pregnancy complications.ICOSL/ICOS is a ligand and receptor of costimulatory signals,which regulates maternal and fetal immune tolerance by participating in T cell differentiation and Th1 and Th2 cytokine secretion.Therefore,this article reviews the structure of ICOSL/ICOS,the distribution of ICOSL/ICOS at the maternal-fetal interface and its immune regulation during pregnancy,in order to provide new ideas for the future study of immunotherapy of pregnancy complications caused by abnormal co-signaling molecules.展开更多
目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD...目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD4+T淋巴细胞上CD28与脾CD19+B淋巴细胞上CD86的表达水平。应用免疫组化法检测同期小鼠肝脏虫卵肉芽肿周围炎性浸润细胞上CD28、CD86表达水平变化。取同期小鼠脾淋巴细胞用SEA进行诱导培养72 h后,采用ELISA法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-13)细胞因子表达水平。采集同期小鼠的血清,应用ELISA法检测血清中SEA特异性抗体IgG及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变动态变化。结果ICOS-Tg小鼠脾CD4+T细胞上CD28和脾CD19+B细胞上CD86的水平与同期野生型FVB/NJ小鼠相比明显升高,且分别在感染4周后(50.57±7.54 vs 40.38±5.43,P<0.05)及在感染12周后(76.46±10.55 vs 65.10±10.17,P<0.05)差异显著。ICOS-Tg小鼠肝脏虫卵肉芽肿的CD28、CD86表达亦高于野生型FVB/NJ小鼠的水平,且分别在感染7周后(0.485±0.094 vs 0.357±0.078,P<0.05)及感染12周后(0.649±0.072 vs 0.537±0.064,P<0.05)差异显著。ICOS-Tg小鼠Th2细胞因子(IL-4、IL-13)水平从感染7周后比野生型FVB/NJ小鼠显著升高(皆P<0.05);ICOS-Tg小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著高于野生型FVB/NJ小鼠的水平(P<0.05、0.01、0.001不等);ICOS-Tg小鼠Th2分化指数与IgG1/IgG2a的比值亦高于野生型小鼠,分别在感染7、12、16、20周后(P<0.05、0.001)及12、16周后(皆P<0.05)具有显著性差异。在整个病程中,ICOS-Tg小鼠肝脏虫卵肉芽肿体积显著大于野生型FVB/NJ小鼠。结论感染日本血吸虫的ICOS-Tg小鼠CD28、CD86表达及其Th2免疫应答显著上调,并伴随肝虫卵肉芽肿病变增强,表明ICOS信号对CD28-CD86信号通路具有一定的调控作用,且在介导Th2极化及肝虫卵肉芽肿的发生、发展中发挥重要作用。展开更多
基金National Natural Science Foundation of China(No.81960283,82072880)。
文摘Co-signaling molecules are molecules whose ligands on the surface of cells interact with receptors on the surface of T cells to convey stimulatory or inhibitory signals to regulate immune responses.Co-signaling molecules play an important role in tumor and autoimmune diseases.Lately,studies have shown that co-signaling molecules are also involved in the regulation of maternal-fetal immune tolerance,and abnormalities of co-signaling molecules may lead to the imbalance of maternal-fetal immune tolerance,resulting in recurrent abortion,eclampsia and other pregnancy complications.ICOSL/ICOS is a ligand and receptor of costimulatory signals,which regulates maternal and fetal immune tolerance by participating in T cell differentiation and Th1 and Th2 cytokine secretion.Therefore,this article reviews the structure of ICOSL/ICOS,the distribution of ICOSL/ICOS at the maternal-fetal interface and its immune regulation during pregnancy,in order to provide new ideas for the future study of immunotherapy of pregnancy complications caused by abnormal co-signaling molecules.
文摘目的探讨上调可诱导共刺激分子(ICOS)信号对感染日本血吸虫小鼠CD28/CD86的表达及Th1/Th2极化的影响。方法建立ICOS转基因(ICOS-Tg)小鼠及野生型FVB/NJ小鼠日本血吸虫病模型,应用流式细胞术分析感染前(0周)和感染后(4～20周)小鼠的脾CD4+T淋巴细胞上CD28与脾CD19+B淋巴细胞上CD86的表达水平。应用免疫组化法检测同期小鼠肝脏虫卵肉芽肿周围炎性浸润细胞上CD28、CD86表达水平变化。取同期小鼠脾淋巴细胞用SEA进行诱导培养72 h后,采用ELISA法检测培养上清中Th1(IFN-γ、IL-12)及Th2(IL-4、IL-13)细胞因子表达水平。采集同期小鼠的血清,应用ELISA法检测血清中SEA特异性抗体IgG及其亚类IgG1、IgG2a的表达水平。应用HE染色法观察小鼠肝脏虫卵肉芽肿病变动态变化。结果ICOS-Tg小鼠脾CD4+T细胞上CD28和脾CD19+B细胞上CD86的水平与同期野生型FVB/NJ小鼠相比明显升高,且分别在感染4周后(50.57±7.54 vs 40.38±5.43,P<0.05)及在感染12周后(76.46±10.55 vs 65.10±10.17,P<0.05)差异显著。ICOS-Tg小鼠肝脏虫卵肉芽肿的CD28、CD86表达亦高于野生型FVB/NJ小鼠的水平,且分别在感染7周后(0.485±0.094 vs 0.357±0.078,P<0.05)及感染12周后(0.649±0.072 vs 0.537±0.064,P<0.05)差异显著。ICOS-Tg小鼠Th2细胞因子(IL-4、IL-13)水平从感染7周后比野生型FVB/NJ小鼠显著升高(皆P<0.05);ICOS-Tg小鼠血清SEA特异性抗体IgG及其亚类IgG1、IgG2a的水平显著高于野生型FVB/NJ小鼠的水平(P<0.05、0.01、0.001不等);ICOS-Tg小鼠Th2分化指数与IgG1/IgG2a的比值亦高于野生型小鼠,分别在感染7、12、16、20周后(P<0.05、0.001)及12、16周后(皆P<0.05)具有显著性差异。在整个病程中,ICOS-Tg小鼠肝脏虫卵肉芽肿体积显著大于野生型FVB/NJ小鼠。结论感染日本血吸虫的ICOS-Tg小鼠CD28、CD86表达及其Th2免疫应答显著上调,并伴随肝虫卵肉芽肿病变增强,表明ICOS信号对CD28-CD86信号通路具有一定的调控作用,且在介导Th2极化及肝虫卵肉芽肿的发生、发展中发挥重要作用。
