CⅡTA基因修饰树突状细胞增强荷肝癌小鼠抗瘤效应  

Enhanced antitumor effect of dendritic cells modified by CⅡTA gene in hepatocellular carcinoma-bearing mice

作　　者：欧启水[1] 林琪[1] 兰斌[2] 郭慈仁[3] 

机构地区：[1]福建医科大学附属第一医院基因诊断研究室,检验科,福建福州350005 [2]福建医科大学附属第一医院肿瘤外科,福建福州350005 [3]福建医科大学附属第一医院普通外科,福建福州350005

出　　处：《细胞与分子免疫学杂志》2005年第5期580-582,586,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：福建省自然科学基金资助项目(No.C0310016);福建省创新医学课题基金资助项目(No.2001-CX-04);福建省卫生厅青年科研基金资助项目(No.2001055)

摘　　要：目的:探讨MHC-Ⅱ类分子反式激活因子(MHCclassⅡtransactivator)CⅡTA基因对树突状细胞(Dendriticcell,DC)表面MHC-Ⅰ/Ⅱ类分子及共刺激分子CD80、CD86的上调作用,为肝癌生物治疗提供新的思路。方法:从小鼠骨髓中大量扩增DC,并用脂质体转染法将小鼠CⅡTA(mCⅡTA)基因转入DC中,用流式细胞术观察转染前、后DC表面MHC-Ⅰ/Ⅱ类分子及CD80、CD86的表达。建立小鼠肝癌模型,将荷肝癌小鼠分为4组,第1组:分别于肝癌组织块周围注入PBS;第2组:未转入mCⅡTA基因的DC;第3组:转入mCⅡTA基因的DC;第4组:转入mCⅡTA基因并经H22肿瘤抗原刺激的DC。每周1次,连续接种3wk,连续7wk动态测量肝癌的大小,观察转染mCⅡTA基因对荷肝癌小鼠抗瘤效应的影响。结果:转染mCⅡTA基因使DC上MHC-Ⅰ/Ⅱ分子的表达率由74.2%/66.7%明显上调为93.6%/91.4%;CD80/CD86的表达率由52.3%/60.5%明显上调为89.7%/91.5%(P<0.05)。免疫接种后,第4组荷肝癌小鼠肝癌组织块的平均面积明显小于第1、2、3组(在第3、4、5、6、7周时,与第1、2组相比较,P<0.05;在第5、6、7周时与第3组相比较,P<0.05)。结论:转入mCⅡTA后,DC表面MHC-Ⅰ/Ⅱ分子及CD80/CD86的表达率明显上调,DC的抗瘤效应增强。本研究为将DC应用于肿瘤的生物治疗提供了新的途径。AIM： To study the effect of MHC class Ⅱ transactivator（C Ⅱ TA ） on the expression of MHC class Ⅰ / Ⅱ molecules, CD80 and CD86 molecules on dendritic cells （ DCs）, and explore using DCs modified by C Ⅱ TA gene in the biotherapy of tumors. METHODS： We transfected the mouse C Ⅱ TA gene by lipofectamine into DCs drived from mouse bone marrow. The expression of MHC class Ⅰ / Ⅱ, CD80, and CD86 molecules was detected by flow cytometry. 40 mice bearing hepatcellular carcinoma were divided into 4 groups： Group 1 were treated with a para-tumor injection of PBS, group 2 DCs, group 3 modified DCs. and group 4 modified DCs pulsed with H22 tumor antigen. Then the antitumor effect of DCs modified by mC ⅡTA was evaluated by measuring the tumor size. RESULTS： After transfection of mC Ⅱ TA, the expression rate of MHC class Ⅰ / Ⅱ molecules of DCs rose from 74.2%/66.7% to 93.6%/91. 4%, and that of CD80/CD86 rose from 52.3%/60.5% to 89. 7%/91. 5%： After immunization, the growth of H22 tumors in group 4 mice was significantly inhibited compared with that in other three groups （ P〈0.05 at3,4, 5, 6, and 7 weeks versus groups 1,2： P 〈0.0.5 at 5,6, 7 weeks versus group 3）. CONCLUSION： The expression of MHC Ⅰ / Ⅱ, CD80 and CD86 on DCs was regulated markedly by transfection of mC Ⅱ TA. mC Ⅱ TA transfection also enhanced the anti-tumor effect of DCs. Our results provided a new method for biotherapy of tumors with DCs.

关 键 词：CⅡTA 树突状细胞 肝癌 MHC分子 小鼠 

分 类 号：R392.12[医药卫生—免疫学]