肝内致T细胞增殖髓系细胞聚集体（iMATEs）是新近发现的一种肝内特有淋巴器官样微结构，其形成的特殊免疫微环境可帮助细胞毒性T细胞（CTL）克服肝内免疫耐受并实现增殖活化，从而发挥其抗病毒功能。目前尚不清楚乙肝病毒（HBV）感染过程中iMATEs的形成受何种机制调控以及其对疾病进程的影响。申请人前期研究发现，调节性T细胞（Treg）极有可能是HBV感染过程中负向调控iMATEs形成的关键细胞。本项目拟以iMATEs为研究肝脏区域免疫特性的切入点，运用规范化临床标本和HBV小鼠模型，从细胞间网络调控的角度研究HBV感染对Treg细胞、iMATEs构成细胞及肝内CTL间相互作用的影响，阐明Treg细胞调控iMATEs形成的效应及其分子机制，解析其与HBV清除进程间的动态关系。本研究将有助于加深对肝脏区域免疫特性及肝脏疾病病理机制的认识，为开发治疗慢性HBV感染的免疫治疗策略提供靶点和理论基础。

The intrahepatic myeloid-cell aggregates for T cell population expansion (iMATEs）are a newly identified lymphoid organ like micro-structure specifically locate in liver. The special immune microenvironment of iMATEs prevents cytotoxic T lymphocytes (CTL) from liver induced immune tolerance and promotes the proliferation, activation and the antiviral function of CTL. It remains unclear how the formation of iMATEs is regulated during HBV infection and how it influences disease progression. The results of our previous study indicate that regulatory T cells (Treg) play an essential role in negatively regulating iMATEs formation during HBV infection. By using standardized clinical human samples and HBV infection mouse models, this project is aimed to study the interaction of Tregs, component cells of iMATEs and intrahepatic CTLs during HBV infection, clarify the effects and molecular mechanisms of regulating iMATEs formation by Tregs, and analyze it is impact on HBV clearance. The results of this project will further increase our understanding of the liver-specialized immunologic features and their interplay with liver diseases and will provide novel targets for immune therapies against liver-associated diseases such as chronic HBV.