慢性乙型肝炎病毒（HBV）感染机制是当前免疫学研究的重点和前沿，研究表明免疫共刺激分子在其中发挥重要作用。BTLA是继CTLA-4、PD-1之后发现的另一个具有负向调节功能的共刺激分子，在调节T细胞免疫以及维持机体免疫平衡方面发挥重要作用。我们前期研究表明BTLA分子在慢性乙型肝炎（CHB）患者中高表达，随着CHB向HBV慢加急性肝衰竭临床进展，CD4+T和CD8+T细胞上BTLA表达呈进行性下降，且与HBV病毒载量呈负相关，提示BTLA与HBV慢性感染密切相关。本课题拟利用临床标本研究BTLA在慢性HBV感染者肝组织以及外周淋巴细胞中的表达水平与特点，同时与HBV感染疾病进程进行相关性分析，在此基础上探讨BTLA对CHB患者外周血T淋巴细胞活化、分泌细胞因子、增殖及凋亡的影响，并进一步运用基因芯片及生物信息分析技术检测并筛选出BTLA作用T淋巴细胞后信号通路表达发生明显改变的相关基因。

The mechanism of chronic hepatitis B virus (HBV) infection is the current focus and cutting-edge of immunology research. Recent studies have shown that the immune costimulatory molecules play an important role in HBV infection. BTLA is a negative costimulatory molecule following CTLA-4 and PD-1 which plays an important role in the regulation of T cell immunity and in maintaining immune balance. Our previous studies have shown that BTLA was highly expressed in the CHB patients and with disease progression from CHB to HBV-related acute on chronic liver failure, the BTLA expression on CD4+T and CD8+T cells showed a progressive decline, and reversely correlated with HBV DNA load, indicating that BTLA was closely associated with chronic HBV infection. The current project will investigate the expression profile of BTLA in liver tissues and peripheral lymphocyte of patients with chronic HBV infection, and analyze the correlation between the expression of BTLA and the disease progression. Furthermore, we will study the effect of BTLA on T cell activation, secretion of cytokine, proliferation and apoptosis. Finally, we will identify the genes associated with the signaling pathways, which were significantly changed in T lymphocytes after stimulated by BTLA by microarray and bioinformatics analysis.