KLRG1介导的T细胞终末分化在机体抗结核免疫反应中的作用及其机制探索

项目名称： KLRG1介导的T细胞终末分化在机体抗结核免疫反应中的作用及其机制探索

项目编号： No.81501365

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡志东

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 杀伤细胞凝集素样受体G1（Killer cell lectin-like receptor G1, KLRG1）是抗病毒免疫应答中短期效应性CD8+ T细胞的分子标记，该分子的表达标志着T细胞进入了终末分化状态。近年来，使用小鼠模型的研究报道提示，KLRG1能够通过调节效应性CD4+ T细胞的终末分化状态，参与机体抗结核免疫应答调控。前期实验中，我们建立了结核病临床研究队列，并利用流式分析技术初步证明，CD4+ T细胞KLRG1的表达水平与感染者的发病情况、多功能细胞因子的分泌能力和细胞活化状态相关。在此基础上，本研究拟进一步通过对细胞增殖能力和分化能力等的检测，评估KLRG1对CD4+ T细胞终末分化状态的调控作用以及抗结核免疫应答的影响。并将从细胞周期信号通路出发，初步探索其调控的分子机制。研究结果将有助于更深入地了解机体抗结核免疫反应，并为设计研发更有效的抗结核疫苗和佐剂提供思路。

中文关键词： 结核分枝杆菌；CD4+；T细胞；终末分化；效应性T细胞；KLRG1

英文摘要： As an indicator of T-cell terminally differentiation in anti-virus infection, killer cell lectin-like receptor G1 (KLRG1) is postulated to be a marker of short-lived effector CD8+ T cells. Recently, it was reported that KLRG1 might contributed to the sustained turnover of terminally differentiated effector CD4+ T cells during chronic Mtb (Mycobacterial tuberculosis) infection in mice. Besides that, our cohort study in TB patients suggests that the expression of KLRG1 on CD4+ T cells is related with TB morbidity through influencing the secretion of multi-functional cytokines and activated state of antigen-specific CD4+ T cells. In this study, we propose to confirm the role of KLRG1 in the terminally differentiation of CD4+ T cells and anti-TB immune responses in our cohort, by further analyzing the function of KLRG1 in cell proliferation and differentiation in responses to Mtb infection. Furthermore, the signaling pathway participated in KLRG1 mediated T-cell terminally differentiation will be explored by starting with the cell cycle pathways. These results will facilitate our understanding of anti-TB immune responses and provide optimism for the development of anti-TB vaccines and adjuvants with greater efficacy.

英文关键词： Mycobacterium tuberculosis;CD4+ T cells;Terminal differentiation;Effector T cells;KLRG1