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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 To investigate the regulatory mechanism of PD-1 molecule on CD8 + T cells in tuberculosis infection. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from four groups of patients (active pulmonary tuberculosis, tuberculosis latent infection, healthy control and primary bronchial carcinoma). The expressions of CD3, CD8 and PD-1 were detected by flow cytometry , The expression of IFN-γ and phosphorylated Stat3, Stat5, P38, Erk1 / 2, and the expression of PD-1 in CD8 + T cells by the expression of surface molecules, intracellular molecules and intranuclear molecules . Results The proportion of PBMCs in PD-1 + CD8 + T cells in active TB group was higher than that in the other three groups with or without Mtb antigen peptide. PD-1 + IFN-γ + CD8 + T cells stimulated with or without Mtb antigen peptide in Active TB were more than PD-1-IFN-γ + CD8 + T cells. PD-1 siRNA was used to silence the expression of PD-1 in patients with active TB, and the IFN-γ production of si RNA-PD-1 group was much less than that of the medium and si RNA-Ctrl groups. The amount of phosphorylated Stat3, Stat5, P38 and Erk1 / 2 was higher in PD-1 + CD8 + T cells than in PD-1-CD8 + T cells. Conclusions PD-1 molecules can induce CD8 + T cells to produce more IFN-γ and show more intracellular activation signal in M. tuberculosis infection.