封闭B7-H1分子对肿瘤浸润树突状细胞介导T细胞免疫功能的影响  

Effects of B7-H1 molecule blockade on tumor-infiltrating dendritic cell-mediated T-cell function

作　　者：陈雅敏[1,2] 梁晓华[1,2] 黄若凡[1,2] 周鑫莉[1,2] 

机构地区：[1]复旦大学附属华山医院肿瘤科 [2]复旦大学上海医学院肿瘤学系和内科学系,上海200040

出　　处：《中国肿瘤生物治疗杂志》2009年第1期50-54,共5页Chinese Journal of Cancer Biotherapy

基　　金：复旦大学附属华山医院科研基金[No.145]~~

摘　　要：目的:研究肿瘤浸润树突状细胞(tumor-infiltrating dendritic cell,TIDC)及脾脏树突状细胞(splenic dendritic cell,SDC)表面B7-H1、B7-1、B7-2分子的表达情况;探讨封闭TIDC及SDC表面B7-H1分子对其介导T细胞免疫功能的影响。方法:CD11c磁珠阳性分选法提取荷瘤小鼠的TIDC及SDC,流式细胞术检测其表面B7-H1、B7-1、B7-2分子的表达情况。TIDC及SDC作为刺激细胞,脾脏T细胞作为反应细胞行混合淋巴细胞反应,同时加入B7-H1抗体或其对照抗体,XTT比色法检测T细胞增殖指数,ELISA法检测T细胞分泌IL-10的量。结果:B7-1及B7-2分子在TIDC表面的表达水平显著低于SDC(P<0.01);B7-H1分子在TIDC及SDC表面皆中度表达,表达水平无明显差异(P>0.05)。TIDC刺激T细胞增殖能力显著低于SDC,且诱导T细胞分泌更多的IL-10。封闭DC表面B7-H1分子后,TIDC刺激T细胞增殖能力显著提高(P<0.01),且诱导T细胞分泌IL-10的量明显减少(P<0.01);SDC刺激T细胞增殖能力及诱导T细胞分泌IL-10的量无明显变化(P>0.05)。结论:封闭DC表面的B7-H1分子能显著提高TIDC活化T细胞的能力,可能解除TIDC介导的肿瘤免疫抑制。Objective：To explore the expression of B7-1, B7-2 and B7-H1 on tumor-infiltrating dendritic cells （TIDC） and on splenic dendritic ceils （SDC） , and to investigate TIDC-mediated and SDC-mediated T-cell function after blocking B7-H1 expression in these dendritic cells. Methods： The TIDCs and SDCs were isolated from tumor-bearing mice using anti-mouse CDllc magnetic beads. The expression of B7-1, B7-2 and B7-H1 on TIDC and SDC was analyzed using flow cytometer. T cells were co-cultured with TIDCs or SDCs for the mixed lymphocyte reaction （MLR） , and monoclonal antibodies to B7-H1 or the isotype control antibodies were added to the MLR cultures. T-cell proliferation was assessed using XTT method and the secretion of IL-10 was detected using ELISA： Results： B7-1 and B7-2 positive TIDCs were significantly less than SDCs （P 〈 0.01 ）. B7-H1 was moderately expressed on both TIDCs and SDCs （P 〉 0.05）. T-cell proliferation stimulated by TIDCs was weaker than that stimulated by SDCs; T cells produced more IL-10 after TIDCs stimula- tion than after SDCs stimulation（P 〈 0.01 ）. After blocking B7-H1 on DCs, TIDCs showed a stronger stimulating ability on T cell proliferation compared with control antibodies, while SDCs did not have significant effect on T cell proliferation and production of IL-10. Conclusion： Blocking B7-H1 on TIDCs can significantly enhance their ability to activate T cells, and may elimilate TIDC-mediated tumor immunosuppression.

关 键 词：肿瘤浸润树突状细胞 T细胞 B7-H1 免疫功能 

分 类 号：R392.1[医药卫生—免疫学] R730.3[医药卫生—基础医学]