脾内途径的肝脏靶向性基因治疗中Kupffer细胞的抗原提呈作用  

The effect on the antigen-presenting function of Kupffer cells by liver-targeting gene therapy

作　　者：李士玉[1] 弭静[2] 徐昌青[1] 李雷[1] 闫明先[1] 曹雪涛[2] 

机构地区：[1]山东省千佛山医院消化内科,济南250014 [2]第二军医大学免疫教研室,上海200433

出　　处：《中国免疫学杂志》2001年第5期239-243,共5页Chinese Journal of Immunology

摘　　要：目的 :探讨肝脏Kupffer细胞 (KC)在脾内途径的肝脏靶向性基因治疗中的抗原提呈作用及可能机制。方法 :以结肠癌肝转移小鼠为模型 ,以脾内移植GM CSF基因修饰的胎肝细胞 (FLC GM)与低剂量IL 2、5 Fu腹腔注射作为基因治疗与化学免疫治疗联合应用方案。结果 :荷瘤小鼠治疗后 2w ,整个肝小叶KC数目均扩增 ;KC对99mTc 亚锡植酸钠吞噬功能明显增强 ;与KC抗原提呈功能和活化T细胞功能密切相关的共刺激分子CD40虽在对照组KC中有基础性表达 ,但在基因治疗联合化学免疫治疗组中 ,其表达水平皆有不同程度的上调 ;此外 ,联合治疗后KC体外能有效诱导同种T细胞增殖反应 ,细胞因子IL 12和IL 12的分泌水平亦升高 ,并且这些反应能被抗CD40L抗体所封闭。结论 :脾内途径的肝脏靶向性基因治疗能有效提高KC的抗原提呈功能 ,CD40The evidernce that Kupffer cells (KC) are capable of controlling metastatic growth in the liver is largely circumstantial.However,the ability of KC to function as antigen-presenting cells was not much studied.Thus,the aim of this study was to characterize the effect on the antigen-presenting function of Kupffer cells by intrasplenic transplantation of GM-CSF gene-modified fetal liver cells (FLC-GM)in combination with IL-2 and 5-Fu.Two weeks after the tumor-bearing mice was treated,strong increase in KC numbers and percentage of phagocytosis of 99m Tc within the liver tissue were observed.At the same time,co-stimulator antigen CD40 expression on KC were determined by fluorescence-activated cell sorter(FACS)and found that its expression level was upregulated.In addition,OVA-specific autogenetic T cells mixed lymphocyte reaction induced by KC have increased.Moreover,we observed that blocking CD40/CD40L interaction with anti-CD40L mAbs caused significantly inhibition of T cell proliferation response and inhibition of IL-2 and IL-12 production.These results indicated that intrasplenic transplantation of GM-CSF gene therapy in combination with immuno-chemotherapy could efficiently activate the KC immunologic function, particularly its antigen-presenting function.

关 键 词：KUPFFER细胞 脾内移植 基因修饰 抗原提呈 肝转移癌 基因治疗 

分 类 号：R735.7[医药卫生—肿瘤] R730.5[医药卫生—临床医学]