联合阻断共刺激信号对移植免疫耐受的影响  

The impact of combinative blockade of costimulatory pathway on the transplant tolerance

作　　者：姜晓峰[1] 张弘彬[1] 郭大伟[1] 孙文郁[1] 金俊哲[1] 马冬岩[1] 赵宇[1] 姜洪磊[1] 梁健[1] 

机构地区：[1]中国医科大学附属第四医院普外科,沈阳110032

出　　处：《中国免疫学杂志》2009年第7期634-637,共4页Chinese Journal of Immunology

基　　金：教育部留学回国人员科研启动基金资助项目;中国医科大学附属第四医院院内课题项目(No.2006J06)

摘　　要：目的:探讨联合阻断共刺激信号对移植免疫耐受的影响。方法:采用野生型BALB/c小鼠作为供体,采用野生型B6小鼠作为受体进行腹部异位小鼠心脏移植。受体接受单独或联合使用抗CD40L抗体(MRl)和抗B7抗体的治疗,以阻断CD28-B7和CD40-CD40L(ligand,配体)共刺激信号。以心脏完全停跳作为排斥反应终结时间,并开腹确认心脏是否停跳。心脏移植后60日对移植物进行HE染色。为确定移植免疫耐受是否具有供体抗原特异性,对接受联合阻断共刺激信号治疗而长期存活的受体实施了第二部分来源(供体来源)及第三部分来源(C3H来源)的皮肤移植。结果:联合阻断共刺激信号使移植心脏长期存活(>150日),而且组织病理学检查未见慢性排斥反应发生。供体来源的皮肤长期存活(>50日),而第三部分来源的皮肤则很快被排斥。结论:联合阻断共刺激信号CD28-B7与CD40-CD40L可诱导出不伴有慢性排斥反应的供体抗原特异性的移植免疫耐受。Objective： To determine the effect of combination of costimulatory signal blockade on transplant tolerance. Methods： The mouse heart transplantation was performed using WT BALB/c mice as donors and WT B6 mice as recipients. The recipients were administrated with anti-CD40L and/or anti-B7 monoantibodies （mAbs） to block the costimulatory pathway of CD28-B7 and/or CD40-CD40 ligand. Rejection was defined as a complete cessation of palpable beat and was confmned by direct visualization after laparotomy. The hematoxylin and eosin staining of cardiac allografts was performed on 60 days after wansplantation. The skin transplantation of second grafts （donor） or third party ori- gin （C3H） were performed on the recipients of long-surviving grafts with combinative blockade of costimulatory signal to determine whether donor-specific transplant tolerance was induced.Results： Combinative blockade of costimulatory signal resulted in long-surviving of heart allograft （ 〉 150 days） and the cardiac allografts showed no chronic rejection development. The donor skin grafts engrafted more than 50 days,however, the third party skin grafts were rejected rapidly. Conclusion： Combinative blockade of CD28-M and CD40-CD40 ligand pathway induces the donor-specific transplant tolerance without chronic rejection.

关 键 词：共刺激信号 小鼠心脏移植 供体抗原特异性 移植免疫耐受 

分 类 号：R392.4[医药卫生—免疫学]