联合阻断CD28/B7与CD40/CD40L共刺激通路诱导抗原特异性免疫耐受  

Blockade of CD28-B7 and CD40-CD40 ligand interactions induces long-term heart allograft survival and donor-specific tolerance in mice

作　　者：顾梅[1] 姜晓峰[1] 关炳星[1] 张昆鹏[1] 

机构地区：[1]首都医科大学附属北京同仁医院移植中心,北京100176

出　　处：《中华器官移植杂志》2007年第10期585-588,共4页Chinese Journal of Organ Transplantation

摘　　要：目的探讨阻断CD28/B7与CD40/CD40L共刺激通路对同种异体小鼠移植心脏存活时间的影响及其机理。方法实验分4组进行,均以C57BL/6小鼠为受者,BALB/c小鼠为供者,施行腹部异位心脏移植,根据分组要求,MRI组于移植当天静脉内注射抗CD40L单克隆抗体(MR1抗体)0.25 mg/d,移植后第2、4天改为腹腔注射0.25 mg/d;抗B7组于移植当天至术后第4天腹腔内注射抗B7-1和抗B7-2抗体各0.1 mg/d;联合处理组术后联合使用MR1抗体和抗B7抗体,二者的用法同MR1组和抗B7组;对照组术后不使用任何抗体。记录各组移植心的存活时间;移植后60d时对移植心脏组织行病理学检查。联合处理组的受者于心脏移植后150 d分别接受供者来源(BALB/c小鼠)及无关供者来源(C3H小鼠)的皮肤移植,对照组的受者也同时接受两种皮肤移植,术后不进行处理,术后观察移植皮片的存活时间。结果对照组移植心脏存活时间为(7.86±1.57)d,与对照组比较.MR1组、抗B7组和联合处理组的移植心脏存活时间均得到显著延长,但联合处理组延长最为明显,均超过150d;MR1组和抗B7组移植心脏组织病理学检查均呈慢性排斥反应改变,而联合处理组未见明显慢性排斥反应征象。联合处理组移植的供者来源皮肤存活时间均超过50 d,而无关供者来源的皮肤则被很快排斥;对照组两种来源的皮肤移植后存活时间均较短。结论联合阻断CD28/B7与CD40/CD40L共刺激通路可延长移植心脏存活时间,诱导出抗原特异性免疫耐受。Objective To investigate the effect of blockade of costimulatory signal on allograft survival in mouse cardiac transplantation. Methods Intra-abdominal heterotopic heart transplantation was performed. The cardiac allograft recipients were treated with MR1 and/or anti-B7 mAbs. Histological changes of heart in the sections stained by hematoxylin and eosin were observed on the posttransplant day 60. To evaluate whether recipients of long-survival grafts （〉150days） with administration of MR1 and anti-B7 showed donor-specific mechanisms of graft acceptance, skin transplantation of second grafts （donor） or third party origin （C3H） were performed. Results The treatment of MR1 and anti-B7 resulted in prolonged heart allograft survival （〉150 days） and the heart allografts showed no development of chronic rejection. Second set donor skin grafts engrafted well （〉50 days）, whereas third party skin grafts were vigorously rejected. Conclusion Blockade of CD28-B7 and CD40-CD40 ligand interactions resulted in long-term allograft survival and donor-specific tolerance in mouse cardiac transplantation without chronic rejection.

关 键 词：抗原 CD80 抗原 CD40 心脏移植 免疫耐受 小鼠 

分 类 号：R617[医药卫生—外科学] R392.4[医药卫生—临床医学]