T淋巴细胞免疫功能重建对小鼠肝癌转移的影响  

Influence of reconstruction of immunological functions of T lymphocytes on mouse hepatocarcinoma me- tastasis

作　　者：王凯峰[1] 叶胜龙[1] 薛琼[1] 宋丽杰[1] 田波[1] 梁春敏[1] 翁永强[1] 汤钊猷[1] 

机构地区：[1]复旦大学肝癌研究所,中山医院,教育部癌变与侵袭原理重点实验室,上海200032

出　　处：《中华肝脏病杂志》2005年第6期443-446,共4页Chinese Journal of Hepatology

基　　金：国家重点基础研究(973)项目(G1998051210)复旦大学"985工程"重中之重学科项目(校批字[2001]10号)复旦大学"211工程"肿瘤学科建设项目(校批字[2003]257号)

摘　　要：目的研究T淋巴细胞免疫功能重建对小鼠肝癌转移程度的影响,进一步探讨免疫对肝癌转移的影响因素,寻找肝癌转移的免疫干预手段。方法建立T淋巴细胞免疫功能重建的模型。将裸鼠分成高、低转移的T淋巴细胞免疫功能重建组和未重建组。取淋巴结通过病理切片观察转移程度。计算成瘤时间和生长速度的差异,检测肿瘤细胞株组织相容性复合物(MHC)Ⅰ、Ⅱ表达。应用Th1—Th2-Th3基因芯片检测不同转移潜能小鼠体内T淋巴细胞相关基因的差异。结果进行T淋巴细胞免疫功能重建后裸鼠外周血CD 3、CD4、CD 8和CD4/CD 8比例均高于未重建组;高、低转移潜能的肝癌细胞在裸鼠体内平均成瘤时间为(7.7±0.6)d,正常Balb/c小鼠为(11.5±1.3)d。高、低转移潜能肝癌细胞的肿瘤生长速度具有明显的差异。免疫重建后的裸鼠肿瘤淋巴结远处转移显著降低(P<0.0 5)。高转移组肿瘤细胞的M H C Ⅰ表达明显低于低转移组(P<0.0 5)。高转移组T淋巴细胞Th1/Th2相关基因的表达低于低转移组。结论免疫功能重建可以在一定程度上影响小鼠肝癌的转移。肿瘤M H C分子表达的改变和机体淋巴细胞T h 1/T h 2 相关基因的表达降低可能是影响肝癌转移潜能的原因。Objective To investigate the effectiveness of reconstruction of immunological functions of T cells on the degree of metastases of mouse hepatocarcinoma and the mechanisms of their functioning. Methods The T cell model of immunological functions in Balb/c nu/nu mice was established and the effectiveness of the model was evaluated. The mice were divided into 4 groups. The immunological functions of T cells in experiment groups of Balb/c nu/nu mice were reconstructed. Metastases of the cancer in lymph nodes in each group were examined histologically. The formation time and growth rate of the tumors were calculated. The expression of MHCI and II of the tumor cell line and the difference of expression of immune associated gene were detected by Th1-Th2-Th3 gene array. Results The ratio of CD3, CD4, CD8 and CD4/CD8 in the reconstructed group was higher than that in the control group. The average formation time was 7.7 ± 0.6 days in Balb/c nu/nu mice and 11.5 ± 1.3 days in Balb/c mice. The extent of metastases of the experiment group was lower than that of the control group (P < 0.05). The expression of MHCI of the high metastasis cell line was lower than that of the low metastasis cell line (P < 0.05). The expressions of Th1/Th2 associated genes in lymphocytes of high metastasis mice were lower than those of the low metastasis mice. Conclusions Reconstruction of the immunological function of T cells can influence the metastasis of mouse hepatocarcinoma. The alteration of MHC molecule and low expression of Th1/Th2 correlated genes in lymphocytes may be a factor influencing the metastasis of liver cancer.

关 键 词：免疫功能重建 T淋巴细胞 肝癌转移 Th1/Th2 组织相容性复合物 Balb/c小鼠 CD4/CD8 淋巴结远处转移 转移潜能 相关基因 基因芯片检测 生长速度 肝癌细胞 肿瘤细胞株 转移组 干预手段 方法建立 病理切片 鼠外周血 免疫重建 

分 类 号：R735.7[医药卫生—肿瘤]