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目的观察IL-4基因转染对HL-60增殖及T细胞功能的影响及其可能机制。方法采用逆转录病毒载体介导基因转染法将人IL-4基因导入髓系白血病细胞HL-60,观察高表达外源性IL-4基因HL-60株的增殖反应及其诱导的正常人PBMC增殖,IL-2、IL-6、IFN-γ基因表达及肿瘤特异性CTL杀伤活性。结果rIL-4或瘤细胞产生的IL-4早期促进HL-60细胞增殖,培养5天后则明显抑制其增殖;与rIL-4处理的HL-60细胞比较,IL-4基因修饰的HL-60细胞明显促进正常人PBMC增殖并合成IL-2、IL-6及IFN-γmRNA,其诱导的特异性CTL杀伤活性明显高于野生型HL-60、仅导入载体的HL-60和加入rIL-4共育的HL-60细胞诱导者。结论IL-4基因转染在影响HL-60细胞增殖和分化过程的同时,可能促进某些抗原(如MHCⅠ类抗原)的抗原性,从而有利于机体建立有效的抗肿瘤免疫反应。
Objective To investigate the effect of IL-4 gene transfection on the proliferation and T cell function of HL-60 and its possible mechanism. Methods Human IL-4 gene was transfected into HL-60 myeloid leukemia cells by retroviral vector-mediated gene transfection method. The proliferative response of HL-60 gene and the normal human induced by it PBMC proliferation, IL-2, IL-6, IFN-γ gene expression and tumor-specific CTL cytotoxicity. Results The IL-4 produced by rIL-4 or tumor cells promoted the proliferation of HL-60 cells at early stage and inhibited the proliferation of HL-60 cells after 5 days of culture. Compared with HL-60 cells treated with rIL-4, IL-4 gene modified HL- The proliferation of normal human PBMCs was significantly enhanced and the levels of IL-2, IL-6 and IFN-γ mRNA were significantly increased in PBMCs. The specific cytotoxic activity against CTLs was significantly higher than that of wild type HL-60 cells and only in HL-60 and rIL-4 Co-incubation of HL-60 cell inducer. CONCLUSION: IL-4 gene transfection may affect the antigenicity of some antigens (such as MHC class I antigens) while affecting the proliferation and differentiation of HL-60 cells, which will help the body to establish an effective anti-tumor immune response.