β-葡聚糖增强乙肝病毒核心抗原诱导特异性CTL反应并抑制HBV复制的作用和机制研究

慢性HBV感染者外周血DC功能缺陷和表型不成熟,导致DC不能有效递呈HBV抗原导致HBV特异性CTL反应缺失或低下是HBV感染慢性化的主要因。有效诱导机体特异性CTL反应是慢乙肝治愈的关键。研究表明，β-葡聚糖能通过调节DC功能、增强特异性CTL杀伤效应抑制肿瘤细胞生长。此外β-葡聚糖可以激活细胞自噬。但β-葡聚糖在慢性HBV感染中对DC功能、CTL杀伤效能及自噬激活的影响尚未见报道。本课题组前期研究中发现含有乙肝病毒核心抗原的腺病毒Adv-HBcAg可以诱导CTL反应抑制HBV复制，本研究拟在前期研究的基础上构建Adv-HBcAg，联合β-葡聚糖旨在诱导更强的HBV特异性CTL反应，构建体外细胞及体内小鼠模型，对DC功能、CTL反应及自噬进行检测，在动物及细胞水平探讨β-葡聚糖在腺病毒Adv-HBcAg诱导HBV特异性CTL反应中的作用及机制，为慢乙肝的免疫治疗提供新的途径和实验基础。

The main reason for the chronicity of HBV infection is that the functional defect and immature phenotype of peripheral blood DC in patients with chronic HBV infection lead to the failure of DC to effectively present HBV antigen and the loss or low specific CTL response. Therefore, effective induction of specific CTL response is the key to cure chronic hepatitis B. Studies have shown that β - glucan can inhibit the growth of tumor cells by regulating DC function and enhancing specific CTL killing effect. Other studies have suggested that β - glucan can induce DC autophagy and affect T cell differentiation. However, the effect of β - glucan on DC function, CTL killing efficiency and autophagy activation in chronic HBV infection has not been reported. Our previous study found that Adv-HBcAg containing hepatitis B virus core antigen can induce CTL reaction and inhibit HBV replication. Therefore, we intend to construct Adv- HBcAg combined with β - glucan on the basis of previous study to induce stronger HBV specific CTL reaction, and detect DC function, CTL reaction and autophagy by constructing cell and mouse models to explore the role and mechanism of β - glucan in promoting HBV specific CTL response induced by Adv -HBcAg, and to provide a new way and experimental basis for immunotherapy of chronic hepatitis B.