Vγ9Vδ2（也称Vγ2Vδ2）T细胞作为一群可识别细菌分泌磷化抗原的主要γδT细胞亚群，在抗结核感染中发挥重要的免疫功能。新型FPPS抑制剂BHP-1236可通过增加体内IPP水平而激活Vγ9Vδ2 T细胞，诱导其发挥抗肿瘤或抗感染作用。我们的前期研究发现，结核患者外周Vγ9Vδ2 T细胞比例发生显著下调，体外扩增的Vγ9Vδ2 T细胞可显著抑制人原代单核巨噬细胞内Mtb的生长复制。我们的科学假说为：BHP-1236可激活体内的Vγ9Vδ2 T细胞并进行大量扩增，通过释放细胞因子和杀伤靶细胞抑制胞内结核菌的生长。本项目拟在细胞和动物水平明确BHP-1236是否能增强Vγ9Vδ2 T细胞的抗结核感染作用，阐明此细胞亚群的效应功能和抑菌机制。这为探讨新的免疫治疗靶点和新药研发提供理论基础。

Vγ9Vδ2 (also called Vγ2Vδ2) T cells play an important immune role in anti-tuberculosis infection as a major group of γδ T cells that can recognize phosphoantigens secreted by Bacteria. New FPPS inhibitors, BHP-1236, can activate Vγ9Vδ2 T cells by increasing IPP levels in vivo, and the cells play an important role for anti-tumor or anti-infection. Our previous studies found that the proportion of peripheral Vγ9Vδ2 T cells in tuberculosis patients was significantly reduced. Vγ9Vδ2 T cells expanded in vitro could significantly inhibit the growth and replication of intracellular Mtb in human primary mononuclear macrophages. Our scientific hypothesis is that Vγ9Vδ2 T cells can be activated by BHP-1236 and proceed to large-scale expansion in vivo to inhibit the growth of intracellular tuberculosis by releasing cytokines and killing target cells. Furthermore, our project will determine whether BHP-1236 can enhance the anti-tuberculosis effect of Vγ9Vδ2 T cells in cellular level and animal level, respectively, and clarify the effect function and antibacterial mechanism of this cell subset. These will provide theoretical basis for exploring new immunotherapy targets and new drugs.