正常的免疫功能可让大部分结核感染呈潜伏状态。免疫功能低下是潜伏性结核转变为活动的重要原因。活动性结核患者体内NK细胞呈抑制状态，提示NK细胞功能受损可能是导致结核由潜伏转变为活动的原因之一。目前，活动性结核患者NK细胞功能受损的机制还不甚清楚。我们在预实验中发现活动性结核患者NK细胞表面Tim-3分子表达显著增高，且Tim-3表达和NK细胞分泌IFN-gamma的能力呈负相关。据此，我们推测Tim-3通路引起的NK细胞功能损伤，是结核分枝杆菌逃避宿主免疫清除以及活动性结核发生的可能原因。本课题拟通过分析潜伏及活动性结核患者Tim-3分子和NK细胞表型及功能的关系，以期证明Tim-3分子表达增加是否和NK细胞失功相关；通过观察阻断Tim-3信号通路后是否能恢复NK细胞活性以及对小鼠结核病模型的影响，来评价其抗结核潜能。本课题可以为进一步明确活动性结核的发病机制及寻找新的治疗靶点提供实验依据。

Our immune system has the ability to inhibit mycobacterium tuberculosis growth and prevent development into active diseases in majority of people. A reduction in immune function is an important reason that leads the latent infection to develop into active disease. Decreased NK cell activity is observed in patients with active tuberculosis, which prompts that abnormality in NK cell activity is one of reasons to cause tuberculosis development. Recently, the mechanism of impaired NK cell activity in active tuberculosis patients is largely unknown. We observed that the expression of Tim-3 on NK cells was significantly increased in active tuberculosis patients, and Tim-3 expression on NK cells was reversely associated with intracellular IFN-gamma production. Thus, Tim-3-induced impairment of NK cell activity is the possible reason why this bacterium can escape from host immune clearance and develop into active disease. To investigate the relationship between Tim-3 expression and abnormality in NK cell activity in tuberculosis patients, the expression of Tim-3 and the phenotype and function of NK cells will be analyzed. Furthermore, to determine the potential therapeutic effect of Tim-3 pathway in tuberculosis, a Tim-3 blocking antibody will be used for analysis of NK cell lytic function and also be administrated in a mouse model of tuberculosis. This research would be a basis for further understanding the development of active tuberculosis, which could be resulted in finding a new potential therapeutic target for the treatment of this disease.