慢性淋巴细胞白血病（CLL）是一种淋巴细胞克隆增殖性疾病，其发病机制目前尚不明确。前期研究证实PD-1在CLL中下调T细胞功能，导致肿瘤发生。本课题组在进一步的研究中发现与PD-1具有等同地位的负性协同刺激分子Tim-3在CLL中表达明显升高。Tim-3作为一种新型的Th1、Th17负性调控分子，与Galectin-9结合可下调Th1及Th17细胞的反应，在自身免疫性疾病和恶性肿瘤发病中起重要作用。为了探索Tim-3/Galectin-9在CLL病程进展中的免疫调控机制，本项目组拟以Tim-3在CD4+和CD8+细胞中的表达为切入点，以T细胞因子为检测靶点，应用质粒转染技术、RNAi干扰技术、受体特异性阻断技术等，从临床实验、细胞培养和动物体内实验三个层面验证CLL疾病状态下Tim-3/Galectin-9对T细胞的免疫调控机制，为Tim-3成为新的治疗靶点提供理论依据。

Chronic lymphocytic leukemia （CLL) is a monoclonal disorder characterized by a progressive accumulation of lymphocytes and its mechanism is not completely clear. Previous studies have shown that PD-1 could down-regulate T cell function in CLL, and cause tumors. In further studies, our group found that the other negative regulatory molecules Tim-3 was significantly increased in CLL. Tim-3, as a new negative regulatory molecule, combined with Galectin-9, can down-regulate the response of Th1 and Th17 cells, and plays an important role on pathogenesis of autoimmune diseases and malignant tumors. Therefore, our research group will detecte the expression of Tim-3 in CD4+ and CD8+ cells and the cytokines of T cells, by using the plasmid transfection, RNAi technology, receptor blocking technology, to validate the immune regulation mechanism of Tim-3/Galectin-9 on T cell and provide the theory basis of its target therapy for CLL.