研究已证实，免疫抑制因素在活动性结核的发病中起着重要作用。我们前期研究发现，PD-1可能作为抑制性因素参与活动性结核的发病。最近在HIV感染的研究中证实，PD-1可以特异性上调AP-1转录因子超家族成员BATF的表达，从而降低T细胞活性。我们同样也发现，活动性结核患者BATF表达升高，且与PD-1相关。因此，推测PD-1可能通过BATF介导其负性调控抗结核免疫反应。本课题将入选不同结核感染状态的人群，包括活动性结核患者、潜伏结核感染者及健康对照者，利用细胞染色和流式细胞术，确定PD-1、BATF的表达及其与结核特异性T细胞功能耗竭的关系；然后通过体外实验体系激活或阻断PD-1通路，了解其对结核特异性T细胞表达BATF的影响；最后利用siRNA技术上调或沉默BATF基因表达，明确BATF对结核特异性T细胞功能的影响，从而为开发以BATF分子为靶标的新型结核免疫治疗提供理论基础。

Studies have showed that inhibitory immunological factors play an important role in the immunopathogenesis of active tuberculosis. Our preliminary study found that PD-1 may act as inhibitory factors involved in the pathogenesis of active TB. Recent study on HIV infection confirmed that PD-1 inhibited T cell function by upregulating BATF (Basic leucine zipper transcriptionfactor,; member of AP-1 superfamily). And we also found that BATF expression in patients with active tuberculosis was significantly higher than those of individuals of latent tuberculosis infection and health controls, which was associated with PD-1 expression in active tuberculosis. Thus, we presume that BATF molecule maybe mediate PD-1 negative regulation of T cell functions in active tuberculosis. Therefore, we are going to enroll subjects with different status of tuberculosis infection, including active and latent infection to determine the relationship between expressions of PD-1 and BATF, and tuberculosis specific T cell exhaustion using cell staining and flow cytometry. Then artificial activation/ blockade PD-1 pathway in vitro will be employed to understand the effect of PD-1 pathway on BATF expression on tuberculosis-specific T cells. And BATF expressions will be regulated by small interfering RNA (siRNA) to elucidate the influence of BATF on tuberculosis specific T cell functions. These findings will be expected to provide theoretical basis for the development of new immunotherapy strategy targeting BATF in tuberculosis.