肝纤维化的发生发展与免疫炎症反应密切相关，但机制不明。我们前期工作证实慢性乙型肝炎患者外周血CD4+T细胞可显著上调表达毒性T淋巴细胞相关抗原-4 (CTLA-4)，并参与调控肝星状细胞（HSCs）的促纤维化特性。HSCs是肝纤维化的核心细胞，且具有抗原递呈功能，可表达共刺激分子B7-1(CTLA-4的配体)。本研究以CTLA-4为切入点，从HSCs和CD4+T细胞间相互作用出发，利用单克隆抗体阻断共培养体系及小鼠肝纤维化模型中CTLA-4及可能的下游分子如CD4+T功能因子IFN-γ、IL-4、IL-17或其配体B7-1，探讨 CTLA-4能否通过影响CD4+T细胞应答或影响CTLA-4/B7-1信号通路调控HSCs的促纤维化特性，及CTLA-4的上述调控功能在肝纤维化进程中的意义。研究结果将有助于我们深入理解炎症和纤维化信号通路之间的联系，为免疫治疗肝纤维化打下坚实理论基础。

Despite the close association of inflammation with liver fibrosis, little is known about their cellular cross-talks. Our previous data indicated peripheral CD4+ cells of CHB patients expressed high levels of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and regulated the pro-fibrotic features of hepatic stellate cells (HSCs). HSCs, the cornerstone of liver fibrosis, express B7-1 (ligand of CTLA-4) and present antigens. Thus, this research is designed to investigate whether CTLA-4 regulates the fibrotic features of HSCs through its effects on cytokine response induced by CD4+ cells (IFN-γ、IL-4、IL-17) or through the direct CTLA-4/B7-1 interaction, and to investigate the significance of these two pathways during liver fibrosis by the additions of monoclonal antibodies to block CLTA-4 and its downstream effector molecules in both in-vitro co-cultures and in-vivo mouse liver fibrosis models. Findings will contribute to our understanding of cross-talks between inflammation and fibrosis signal pathways, and make a theoretical foundation for future immunotherapy of liver fibrosis.