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结核感染中PD-1调节CD8^+T细胞免疫应答的研究 被引量:6

Study on CD8^+T cell immune response regulated by PD-1 in Mycobacterium tuberculosis infection
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摘要 目的了解结核感染中程序性死亡因子-1(PD-1)分子对CD8+T细胞的调节机制。方法分离四组病人(活动性肺结核病人、结核潜伏感染病人、健康控制对照、原发性支气管癌病人)的外周血单个核细胞(PBMCs),应用流式细胞术检测CD3、CD8、PD-1、IFN-γ及磷酸化Stat3、Stat5、P38、Erk1/2分子的表达,通过四组病人表面分子、胞内分子及核内分子的表达,了解PD-1在CD8+T细胞中的调节作用。结果活动性肺结核病人(Active TB)组在经或未经结核分枝杆菌(Mtb)抗原肽刺激下PD-1+CD8+T细胞所占PBMCs比例都高于其他三组。Active TB中经或未经Mtb抗原肽刺激的PD-1+IFN-γ+CD8+T细胞多于PD-1-IFN-γ+CD8+T细胞。用PD-1的si RNA来沉默Active TB病人PD-1的表达,si RNA-PD-1组产生的IFN-γ远远少于Medium组和si RNA-Ctrl组。PD-1+CD8+T细胞表达磷酸化Stat3、Stat5、P38和Erk1/2的量高于PD-1-CD8+T细胞。结论结核分枝杆菌感染中PD-1分子能诱导CD8+T细胞产生更多的IFN-γ且表现出更强的细胞内活化信号。 Objective This study aims to investigate the regulation mechanism of programmed death-1(PD-1) on CD8+T cells in Mycobacterium tuberculosis infection. Methods Peripheral blood mononuclear cells(PBMCs) were isolated from four groups(active tuberculosis patients,latent tuberculosis infection, healthy control, and primary bronchogenic carcinoma).Flow cytometry was used to detect the expression of CD3, CD8, PD-1, IFN-γ and phosphorylated Stat3, Stat5, P38 and Erk1 / 2 molecules. Results The frequency of PD-1+CD8+T cells with or without the stimulation of Mycobacterium tuberculosis(Mtb) antigen peptide in active tuberculosis patients(Active TB) was far higher than those of other three groups. In Active TB with or without the stimulation of antigen peptide, the frequency of PD-1+IFN-γ+CD8+T cells was far higher than PD-1-IFN-γ+CD8+T cells. The secretion of IFN-γ of si-RNA-PD-1 group in Active TB was far less than medium and si RNA-Ctrl groups. The expression of levels of phosphorylated Stat5, Stat3, P38 and Erk1 / 2 in PD-1+CD8+T cells were higher than those in PD-1-CD8+T cells. Conclusion PD-1 signaling may induce CD8+T cells to produce more IFN-γ and show stronger intracellular activated signal in Mycobacterium tuberculosis infection.
出处 《热带医学杂志》 CAS 2015年第5期587-591,共5页 Journal of Tropical Medicine
基金 "十二五"传染病防治科技重大专项(2013ZX10003001)
关键词 程序性死亡因子-1 CD8 活动性肺结核病人 IFN-γ PD-1 CD8 active TB IFN-γ
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