干扰素-γ增强肝癌细胞对CTL杀伤敏感性的研究

Study on the susceptibility of the hepatocarcinoma cell to DC-derived CTL lysis under the stimulation of interferon-γ

目的:探讨干扰素-γ(interferon-γ,IFN-γ)能否增强肝癌细胞对树突状细胞(dendritic cell,DC)诱导细胞毒T淋巴细胞(cytotoxic T lymphocyte,CTL)杀伤的敏感性,以及该作用与肿瘤细胞HLAⅠ类分子的关系。方法:RT-PCR法检测IFN-γ刺激前后肝癌细胞β2-微球蛋白(β2-microgloblin,β2-m)的mRNA水平变化,流式细胞术检测肝癌细胞HLAⅠ类分子HLA-A2的表达;应用脐血来源的致敏DC诱导CTL细胞毒试验,观察IFN-γ在增强肝癌细胞对特异性CTL杀伤作用敏感性中的作用。结果:IFN-γ可刺激肝癌细胞上调β2-mmRNA水平及细胞表面HLA-A2表达,IFN-γ作用48h后肝癌细胞β2-m mRNA相对光密度值(1.104±0.209)与0h组(0.674±0.135)比较显著增加,t=-2.992,P=0.040。在72和96h仍保持较高水平,其HLA-A2表达增加的幅度与β2-m一致;致敏的脐血来源DC能够在体外诱导CTL特异性地杀伤肝癌细胞,经IFN-γ刺激的肝癌细胞对特异性效应细胞杀伤作用的敏感性显著增强。结论:IFN-γ可使肝癌细胞对DC诱导的CTL杀伤效应的敏感性增加,可能与其上调肝癌细胞β2-m mRNA水平进而增加HLAⅠ类分子的表达有关。

OBJECTIVE:To study whether interferon-γ can enhance the specific CTL lysis of the tumor cells and its effect on the HLA-I molecules of the tumor cells. METHODS: The mRNA level of β2-microgloblin(β2-m) in the tumor cell were detected by RT-PCR. The expression of HLA-A2 on the tumor cells were detected by flow cytometry. Lymphocytes were primed by DCs, which were derived from cord blood and pulsed with whole tumor cell lysates. The susceptibility of the hepatocarcinoma cell to CTL lysis under the stimulation ...