混合皮肤移植中自体角朊细胞转染B7-1后诱导抑制功能的改变  

The Effects of MHC Ⅱ Molecule and Typical Costimulatory in Immuno-suppression Induced by Auto-keratinocytes in the Intermingled Skin Grafting

作　　者：曹颖平[1] 张敬喜[1] 刘秀琴[1] 郑泽铣[2] 李宁丽[2] 沈佰华[2] 周光炎[2] 

机构地区：[1]福建医科大学附属协和医院检验科,福州350004 [2]上海第二医科大学,上海市免疫学研究所上海200025

出　　处：《福建医科大学学报》2005年第3期269-272,共4页Journal of Fujian Medical University

基　　金：福建省自然科学基金资助项目(C0210012);福建省卫生厅青年基金资助项目(2002110);福建医科大学研究发展基金资助项目(FJGXY04034)

摘　　要：目的分析混合皮肤移植中自体角朊细胞转染B71基因后功能的改变,并探讨传统共刺激分子和MHCⅡ类分子等在自体角朊细胞诱导的局部免疫耐受中的作用。方法利用建立的MELC体外模拟系统,对自体角朊细胞进行B71基因的转染,观察转染前后自体角朊细胞诱导抑制能力的变化,同时通过抗CTLA4单抗及HLAⅡ类分子的封闭实验,观察这些分子在自体皮岛抑制效应中的作用。结果自体角朊细胞转染B71基因后,诱导局部免疫抑制的能力消失,如果加入抗B71单抗阻断B71的作用后,其诱导抑制的能力又恢复;抗CTLA4单抗不能阻断自体角朊细胞在实验体系中的抑制作用;用单抗所作的封闭实验结果表明,抗HLADR单抗封闭组对自体角朊细胞对MELR抑制诱导的影响最小(P>0.05),抗DQ单抗则可以对MELR的抑制得到最大幅度的回复,而抗DP单抗也可以使体系中cpm值有一定的回升。结论混合皮肤移植中,自体角朊细胞之所以可以诱导局部免疫耐受,是通过B71以外的其他共刺激信号激活Th2亚群、进而遏制Th1亚群来诱发抑制的,而且这种抑制与CTLA4的负向调节无关,并具MHC限制性。Objective To explore the effects of typical costimulatory and MHC Ⅱ molecule in local immuno-suppression induced by atuo-keratinocytes（auto-Kc） in the intermingled skin grafting. Methods A testing system based on the mixed epidermal cells-lyrnphocytes culture （MELC） superimposed with autologous epidermal eells（Ea） was established in our lab to mimic local immuno-suppression effect in vivo, and then observed the change of down regulatory ability of auto-keratinocytes when transfected with B7-1 gene and added with mAb against CTLA-4 and MHC Ⅱ molecule in MELC system. Results When transfected with B7-1 gene, the Kc cells lost their down regulatory ability, which could be renewed if anti-B7-1 mAb was introduced. And it was no effect to the allo-reaction when MELC system were added with mAb against typical down regulator-CTLA-4. In addition, blocking experiments with mAb against the HLA-DR, DP and DQ molecule indicated that HLA-DQ and HLA-DP were the critical factors in the local immuno-suppression induce by auto-Kc. Conclusion Above result show that the auto-Kc activated the Th2 cells by indirect recognition pathway, in which costimulaory signal was provided by a kind of molecule different from B7-1, and then inhibited the proliferation of the Th1 cells, leading to a local immuno-suppression for allo-rejection. These local immuno-suppression induced by auto-Kc is independent of CTLA-4 regulation and possessed the character of the restriction of MHC Ⅱ molecule.

关 键 词：混合皮肤移植 角朊细胞 B7-1 免疫抑制 

分 类 号：R392[医药卫生—免疫学]