4-1BBL介导逆向信号在HL-60细胞对淋巴细胞活性影响中的作用

    The role of 4-1BB ligand signal in the effect of the HL-60 tumor cells on lymphocytic activity

    • 摘要: 目的:观察4-1BBL介导逆向信号对HL-60细胞表达肿瘤生长因子-β(TGF-β)的影响,以及阻断4-1BB/4-1BBL信号前后的HL-60细胞培养上清液对淋巴细胞活化、增殖和凋亡诱导作用的影响,探讨肿瘤的免疫逃逸机制。方法:流式细胞术检测HL-60细胞4-1BBL表达水平和阻断4-1BBL信号前后HL-60细胞TGF-β表达水平;将阻断4-1BBL前后的HL-60细胞培养上清液加入淋巴细胞培养液中,流式细胞术检测淋巴细胞活化、凋亡水平,MTT法检测淋巴细胞增殖水平。结果:HL-60细胞表面4-1BBL表达率为92.6%;阻断4-1BBL后的HL-60细胞表达TGF-β水平下降(P<0.05),其细胞培养上清液对淋巴细胞活化没有明显影响(P>0.05),但对淋巴细胞增殖抑制作用和诱导凋亡作用下降(P<0.05和P<0.01)。结论:表达在HL-60细胞表面的4-1BBL可介导逆向信号,通过调节TGF-β分泌抑制机体淋巴细胞活性,为肿瘤细胞的生存创造条件。

       

      Abstract: Objective: To observe the function of the 4-1BB/4-1BBL signal in production of TGF-β in vitro,as well as the influence of HL-60 cells' culture supernatant on T lymphocyte activation,proliferation and inducing apoptosis after blocking 4-1BB/4-1BBL signal.To explore the mechanism by which tumors escape from immunosurveillance.Methods: The expression of 4-1BB ligand and the production of TGF-β in HL-60 tumor cells were analyzed by flow cytometry (FCM);using different concentrations of HL-60 tumor cells culture supernatant which been blocked 4-1BB/4-1BBL signal on lymphocyte,the cell proliferation rate was determined by methyl thiazoly tetrazolium (MTT),the cell apoptosis and CD69 were analyzed by FCM.Results: The level of 4-1BBL expressed on HL-60 was 92.6%.Compared with non-blocking 4-1BB/4-1BBL signal,the production of TGF-β in tumor cells was decreased (P<0.05),the effect of culture supernatant of HL-60 cells inhibited lymphocyte proliferation and induced it apoptosis was decreased (P<0.05 and P<0.01),but there was no significant influence on activation of lymphocytes (P>0.05).Conclusions: 4-1BBL has a reversely regulatory function to induce TGF-β production of HL-60 cells and enhance HL-60 tumor cells to inhibit lymphocyte activity,by which tumor cells can escape from the immune surveillance of tumor-bearing host.

       

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