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。
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-6 and then analyzed the capacity of IFN-ν secretion by NK cells upon stimulation with ESAT-6. Our results indicated that a considerable amount of IFN-ν secreting 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-νupon stimulation （0.09 % ±0.01% ）. Furthermore, IFN-ν production was dramatically variable in two subsets of NK cells. CD56high CD16dim NK ceils exhibited elevated ability to produce IFN-ν（6.50%±0.94%） compared with CD56dlmCD16high NK cells （1.78%±0.38%） when encountering the antigens. With more percentage of IFN-ν secretion by NK cells than that of T cells, NK cells and CD4＋T cells syner gistically correlated in the capacity of IFN-ν secretion. Taken together, our study reported the enhanced cytokine secretion of NK cells in the periphery of active tuberculosis upon Mtbspecific 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.
出处
《现代免疫学》
CAS
CSCD
北大核心
2014年第4期265-271,共7页
Current Immunology
基金
卫生部国家科技重大专项(2013ZX10003007-003-003)
上海市教委重点学科(J0507)
