【摘要】 为了探讨自然杀伤(nature killer,NK)细胞在抗结核免疫应答中的特征,我们表达并纯化结核分枝杆菌特异性抗原蛋白ESAT-6,体外刺激结核病患者和正常人外周血单个核细胞(PBMC),采用流式细胞术分析不同亚群NK细胞IFN-γ释放,并与T细胞释放IFN-γ水平进行相关性分析。结果显示,经结核特异性抗原ESAT-6刺激后,结核患者来源的PBMC中有2.80%±0.65%的NK细胞可以释放IFN-γ,而正常人NK细胞释放的比例仅为0.09%±0.01%,两者间有显著差异(P<0.001);同时CD56highCD16dim NK亚群细胞分泌IFN-γ的水平(6.50%±0.94%)显著高于CD56dimCD16high NK亚群细胞(1.78%±0.38%);比较同一抗原刺激条件下T细胞释放IFN-γ的能力,显示NK细胞释放IFN-γ的能力高于CD4+T和CD8+T细胞,并与释放IFN-γ的CD4+T细胞的比例呈显著正相关。上述研究结果表明,NK细胞在结核特异性抗原ESAT-6刺激下可通过分泌高水平的IFN-γ协同CD4+T细胞在抗结核感染中发挥重要作用,增强NK细胞的功能,以提高结核病患者的免疫应答水平,将为结核病的治疗提供新的策略。更多还原

【Abstract】 To investigate the immunological properties of nature-killer(NK)cells in active tuberculosis,we have expressed and purified the Mycobacterium tuberculosis(Mtb)specific protein ESAT-6and then analyzed the capacity of IFN-γsecretion by NK cells upon stimulation with ESAT-6.Our results indicated that a considerable amount of IFN-γsecreting NK cells(2.80%±0.65%)was detectable in active tuberculosis patients whereas very few NK cells from healthy controls displayed the capacity to secrete IFN-γupon stimulation(0.09%±0.01%).Furthermore,IFN-γproduction was dramatically variable in two subsets of NK cells.CD56highCD16 dimNK cells exhibited elevated ability to produce IFN-γ(6.50%±0.94%)compared with CD56dimCD16 high NK cells(1.78%±0.38%)when encountering the antigens.With more percentage of IFN-γsecretion by NK cells than that of T cells,NK cells and CD4+T cells synergistically correlated in the capacity of IFN-γsecretion.Taken together,our study reported the enhanced cytokine secretion of NK cells in the periphery of active tuberculosis upon Mtb-specific antigen stimulation.More importantly,NK cells orchestrate the cellular immunity against tuberculosis with CD4+T cells,which might become a new biological treatment strategy for active tuberculosis in the future.更多还原