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激活T细胞在机体清除肿瘤细胞起主要作用,然而激活T细胞在杀灭肿瘤细胞的同时也伴有自身凋亡,在肿瘤治疗中难以达到足够数量激活的T细胞来杀灭肿瘤细胞,因此,阻断激活T细胞凋亡,增加激活T细胞数量,有望提高肿瘤免疫治疗的疗效.本研究应用CD3诱导Jurkat细胞系凋亡作为激活T细胞凋亡模型,应用逆转录病毒载体将反义ICE转染Ju-rkat,观察反义ICE对CD3及抗Fas单抗诱发Jurkat细胞的凋亡影响.为此本研究构建了一个反义ICE的逆转录病毒载体(pPS-3-neo-反义ICE),并转染Jurkat细胞系,发现Jurkat细胞ICE蛋白表达量下降,并部分阻断CD3及抗Fas单抗诱导Jurkat凋亡.这些结果表明应用反义技术可阻断ICE基因表达,并部分阻断CD3及抗Fas单抗诱导Jurkat细胞凋亡,因此,应用反义ICE进行基因治疗可望阻断激活T细胞凋亡,提高肿瘤的免疫治疗疗效.
Activation of T cells plays a major role in clearing tumor cells in the body. However, activation of T cells kills tumor cells along with auto-apoptosis. It is difficult to achieve a sufficient number of activated T cells to kill tumor cells in tumor therapy. Blocking the activation of T cell apoptosis and increasing the number of activated T cells is expected to improve the efficacy of tumor immunotherapy. In this study, CD3 was used to induce apoptosis in Jurkat cell lines as a model for activating T cell apoptosis. Antisense ICE was transferred using retroviral vectors. The effect of antisense ICE on the apoptosis of Jurkat cells induced by anti-CD3 and anti-Fas monoclonal antibodies was observed. For this study, an antisense ICE retroviral vector (pPS-3-neo-antisense ICE) was constructed. , And transfected Jurkat cell line, found that Jurkat cell ICE protein expression decreased, and partially blocked CD3 and anti-Fas monoclonal antibody induced Jurkat apoptosis. These results suggest that antisense technology can block the ICE gene expression, and partially blocked CD3 and anti-Fas monoclonal antibody induced apoptosis in Jurkat cells. Therefore, antisense ICE gene therapy is expected to block activation of T cell apoptosis and improve the efficacy of tumor immunotherapy.