γδ T细胞在脓毒症免疫抑制中的作用及其分子机制研究

项目名称： γδ T细胞在脓毒症免疫抑制中的作用及其分子机制研究

项目编号： No.81471848

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李虹

作者单位： 四川大学

项目金额： 75万元

中文摘要： 脓毒症（sepsis)治疗是现代危重病医学面临的突出难题，通过免疫干预提高脓毒症救治水平是当今倍受关注的研究热点。 γδ T细胞是-类功能独特的T淋巴细胞新亚群，在机体抗感染、抗肿瘤及免疫调节功能中发挥重要作用。本课题拟通过当今先进的细胞分离、培养及测试手段，首先研究在脓毒症病理状态下γδ T细胞的数量及功能特征变化，包括脓毒症患者γδ T细胞对特定抗原的应答能力以及γδ T细胞与NK细胞、单核细胞的相互作用关系；并通过细胞凋亡、增殖及信号通路等技术探讨γδ T细胞功能变化的分子机制；同时课题也将进一步研究脓毒症患者γδ T细胞的体外增殖方法以及由此获得的 γδ T细胞的生物学功能，探索以γδ T细胞为切入点纠正脓毒症免疫抑制状态的可能性。该研究是一项基础与临床密切结合的课题，资源珍贵，所获结果对阐明脓毒症的免疫抑制机制、探索免疫干预治疗新措施都具有特别重要的意义。

中文关键词： 脓毒症；γδ；T细胞；免疫抑制；细胞因子

英文摘要： Sepsis therapy is a prominent problem of the modern critical care medicine, and improving the level of sepsis treament by immune intervention measures is a hot research topic with close attention. Gammadelta T cells is considered as one new T lymphocyte subset in recent years, which playing an important role in resistance to infection, anti-tumor and immune regulating function in the body. First, we payed attention to the function characteristics of gamma delta T cells in peripheral blood of sepsis patients including differentiation marker, subtype and production of related cytokine, and then the molecular mechanism of insufficient gamma delta T cells. At the same time the responsibility of gamma delta T cells of sepsis patients to certain bacteria and viral antigen and the regulation of gamma delta T cells on other natural immune cells including of NK cells and mononuclear cells were studied to identify the status and role of gamma delta T cells in sepsis immunosuppression by culture in vitro; further we studied the effect of specific stimulants on proliferation and activation of gamma delta T cells in patients with sepsis and also the anti-infection acquired by gamma delta T cells, expecting as an entry point to explore new treatment strategy to sepsis.This study is a basic and clinical combined closely with the subject, precious resources. Our research has important significance on elucidating the mechanism of immunosuppression of sepsis and exploring new treament strategy of immune intervention to sepsis.

英文关键词： sepsis;γδ T cell;immunosuppression;cytokine