T细胞Sema4D表达在HBV慢性持续感染中的作用机制研究

项目名称： T细胞Sema4D表达在HBV慢性持续感染中的作用机制研究

项目编号： No.81500454

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： 张久聪

作者单位： 中国人民解放军联勤保障部队第九四〇医院

项目金额： 18万元

中文摘要： T细胞免疫在控制和清除HBV感染中发挥关键作用，但是HBV感染导致T细胞功能低下，严重阻碍了机体免疫应答对HBV复制的抑制，其具体机制尚不清楚。Sema4D是近年新发现的免疫调节分子，在免疫系统中T、B细胞的活化和免疫调节中发挥重要作用。研究表明，慢性病毒感染中病毒特异性T细胞的应答低下和Sema4D的表达下调或缺失相关。我们初步研究发现，慢性HBV感染者PBMC中表达Sema4D的T细胞比例较急性HBV感染者和健康对照者显著降低，提示Sema4D可能与HBV感染T细胞功能低下相关。本项目拟进一步研究急、慢性HBV感染者体内不同T细胞亚群Sema4D的表达及其与相应病毒学、免疫学指标的关联，探讨Sema4D表达对T细胞免疫活性的调节作用及对相关细胞因子分泌的影响，揭示Sema4D在HBV感染T细胞应答中的作用，为阐明HBV慢性持续感染分子机制提供实验依据，为抗HBV治疗提供新的思路和靶点。

中文关键词： Sema4D；；T细胞；乙型肝炎病毒；慢性感染；表达

英文摘要： T cell immunity plays a pivotal role in the viral control and clearance in viral hepatitis B infection. HBV infection resulted in T cell dysfunction, impaired T cell response hindered inhibition of HBV replication by host immune response, while the exact mechanism remained unclear. Sema4D which was the first immune semaphonrin discovered played important immune regulatory functions in the mutual activations of T cell and B cell. To date, accumulating evidences have indicated that expressions of Sema4D on T cells were decreased or lost during chronic viral infection. Our preliminary study had found significantly lower level of Sema4D on T cells in patients with chronic hepatitis B infection than in patients with acute hepatitis B infection and in healthy blood donors, which suggested that Sema4D may be a contributory factor in T cell dysfunction in chronic HBV infection. The current study is designed to recruit different stages of HBV-infected subjects and evaluate the expression levels of Sema4D in HBV infection and analyze the correlations among Sema4D expression and corresponding virological and immulogical parameters, and investigate the effects of Sema4D on T cell response and cytokine secretion. Elucidation of the role of Sema4D in T cell response will reveal the mechanism of T cell dysfunction in HBV infection and provide an effective immune strategy for modulating antiviral immunity and treating chronic viral infection.

英文关键词： Sema4D ;T cell;hepatitis B virus;chronic infection;expression