自体灭活T细胞免疫下调调节性T细胞的机理与应用研究

项目名称： 自体灭活T细胞免疫下调调节性T细胞的机理与应用研究

项目编号： No.30872990

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 李宁丽

作者单位： 上海交通大学

项目金额： 30万元

中文摘要： 调节性T细胞（Treg）是调节、维持机体免疫平衡的重要细胞亚群，但是目前发现Treg在肿瘤细胞介导的免疫抑制中起极其重要的作用，也是导致现有肿瘤生物治疗效果不佳的重要因素。去除肿瘤患者体内Treg可以明显增强机体抗肿瘤免疫。本项目组在国际上首次报道采用小鼠自体灭活T细胞免疫可明显下调Treg，导致Th1细胞功能增加、CTL和NK的杀伤功能增强、使接种于小鼠的肿瘤细胞生长减慢、小鼠存活期延长。本项目拟在此原创性研究基础上，从该免疫对于Treg的标志性转录因子Foxp3的调控和相关信号转导机制研究入手，重点探索TLR4的调控作用，以阐明自体灭活T细胞免疫下调Treg的机制和作用靶点，并筛选能够单独或协同本免疫下调Treg的天然小分子化合物。为进一步研究增强肿瘤生物治疗效果提供新靶点、为本原创性研究早日用于临床抗肿瘤治疗提供理论依据和试验基础。因此具有潜在的重大科学意义和应用价值。

中文关键词： 调节性T细胞（Treg）；肿瘤免疫；自体灭活T细胞；Foxp3；TLR4

英文摘要： Regulatory T cells (Treg) are found to play a very important role in inducing and maintaining peripheral tolerance and maintain homestasis. Recently, it is believed that Treg involved in enhancing tumor growth in vivo by inhibiting immune response and imparied efficacy of tumor biotherapy. Using anti-CD25 antibody to delete Treg from patients with tunor has shown obviously effect to enhance anti-tumor immunity in some studies. We have reported firstly in the world that immunization with attenuated autologous mouse T cell can down-regulate Treg in vivo which resulted in that immunized mice arresed tumor growth in vivo by producting more Th1 cytokines, enhancing CTL and NK cytotoxicity. But how and mechanisms of immunization reducing Treg is unknown. In this study, we try to address how Treg is down regulated by the immunization. Whether the immunization involve in the regualtion of Treg nuclear factor Foxps. Whether TLR4 molecule involves in the Foxps regualtion. Moreover, we try to figure out whether there are some nature small molecules can enhance our immunizaiton efficacy by imparied Treg function in vivo. Hofully, through the project, we can point out the mechanisms and find new targets to enhance anti-tumor immunity which to further usful in the clinical study.

英文关键词： Regulatory T cell (Treg)；Tumor immunity； autologous attanuated T cell；Foxp3；T like receptor 4(TLR4)