IL-2和IL-12的单/联合基因治疗对肝癌大鼠体内IL基因表达和T细胞亚群的影响

目的:探讨大鼠诱发性肝癌模型中脾内直接注射IL-2和(或)IL-12基因对血清IL-2和IL-12,以及T细胞活性的影响.方法:全部肝癌大鼠(以二乙基亚硝胺诱发制备)48只分为4组(空载对照组、IL-2单基因治疗组、IL-12单基因治疗组、IL-2/IL-12联合基因治疗组),构建携带IL-2和(或)IL-12基因的逆转录病毒载体及其包装细胞,含IL-2和(或)IL-12基因的包装细胞于不同时间对诱发性肝癌大鼠进行脾内注射转染细胞,比较大鼠血清IL-2和IL-12浓度、T细胞活性和毒性反应.结果: IL单基因治疗后血清IL-2或IL-12明显增高,IL-2/IL-12基因联合治疗组中血清IL较单基因组显著增高(P<0.01),病理示肝癌组织中淋巴细胞浸润明显增多.IL单基因治疗组T细胞活性较对照组显著增高,IL-2/IL-12基因联合组T细胞功能较IL单基因组增强,且持续时间长.结论: 脾内直接注射IL-2和(或)IL-12基因可增强T细胞活性,IL基因联合治疗优于IL单基因治疗.

Effect of IL-2 and/or IL-12 gene therapy on IL gene expression and T cell subpopulation in rats with liver cancer

Objective: To study the effects of intrasplenic injection of IL-12 and/or IL-2 genes on serum levels of IL-2 and IL-12 and T cell activity in induced liver cancer in rats. Methods: Forty-eight rats with diethylnitrosamine induced liver cancer were equally divided into 4 groups: mock-infected group, IL-2 group, IL-12 group and IL-2/IL-12 group. Retroviral vectors encoding IL-2 and/or IL-12 genes were constructed and were used to transfect packaging cell lines PE501 and PA317. The tansfected PE501 and PA317 cells were injected into rat spleen at different time points and the serum levels of IL-2 and IL-12, T cell activity and toxic effect were determined. Results: The serum levels of IL-2 and IL-12 were obviously increased in IL-2 and IL-12 group, respectively, and the increase was even more obvious in IL-2/IL-12 group. Pathological study showed that there was an increase in lymphocytes infiltration of liver tissues in IL-2/IL-12 group. Compared with mock-infected group, T cell activity markedly increased in IL-2 and IL-12 group, and that in IL-2/IL-12 group was even more active. Moreover, the acting time of IL-2/IL-12 was longer than that of IL-2 or IL-12 alone. Conclusion: Direct injection of IL-2 and/or IL-12 genes into spleen can increase the T cell activity. Combined gene therapy with IL-2 and IL-12 is superior to IL-2 or IL-12 gene alone.