联合阻断CD28和ICOS对兔高危角膜移植排斥反应的影响

Simultaneous blockade of inducible costimulator and CD28 pathway on prevention of rabbit corneal allografts rejection

目的:建立兔角膜移植高危模型,通过联合阻断CD28和ICOS,探讨CTLA4-Ig及ICOSmAb对角膜移植排斥反应的影响。方法:实验动物随机分成4组,每组10只。联合阻断组:植片为浸入含有CTLA4-Ig和ICOSmAb的中期保存液中。ICOS组:植片为浸入含有ICOSmAb的中期保存液中。CTLA4组:植片为浸入含有CTLA-4Ig的中期保存液中。对照组:单纯角膜移植,不做CTLA-4Ig和ICOSmAb处理组。观察术后受体植片角膜混浊情况和植片病理改变,RT-PCR方法检测植片IL-2,IL-10mRNA的表达情况,应用流式细胞仪检测植片CD4+,CD8+T淋巴细胞表达情况。结果:联合阻断组兔角膜移植片存活时间(92±18)d,较其它3组明显延长(P<0.05);术后21d联合阻断组移植物中IL-2mRNA表达明显降低(P<0.05),CD4+,CD8+T淋巴细胞表达明显降低(P<0.05);植片组织病理学检查淋巴细胞浸润较其它3组明显减少。结论:应用CTLA4-Ig和ICOSmAb联合阻断CD28和I-COS,可以明显抑制高危角膜移植排斥反应,提高移植的存活率。

AIM： To study the effects of co-stimulatory blockade with anti-inducible co-stimulator antibody in conjunction with CTLA4-1g on prevention of rabbit corneal allograft rejection. METHODS： Experimental animals were divided into 4 groups in random, 10 rabbits for each group. The group of dealing with CTLA4-1g and ICOSmAb, donor corneal preserved in Optisol with CTLA4-1g and ICOSmAb; the group of dealing with ICOSmAb, donor corneal preserved in Optisol with ICOS- mAb; the group of dealing with CTLA4-Ig, donor corneal preserved in Optisol with CTLA4-1g; Control group： simple corneal transplantation, not with CTLA4-1g and ICOSmAb. Evaluate the degree of corneal opacity and the change on histology. The expression of CD4＋ and CD8＋ T cell was detected by flow cytometry. The expression of IL-2 and IL-10mRNA was detected by RT-PCR. RESULTS： Compared with others, survival time of CTLA4-1g and ICOSmAb group （92±18）d was obviously prolonged, and IL-2mRNA expression was obviously difference （P〈0.05）, the numbers of CD4＋ and CD8＋ T cell was obvious down-regulation on the day 21 after transplantation, the number of lymphocyte decreased in the group of dealing with CTLA4-1g and I COSmAb viewing through histology examination. OONCLUSlON： These findings demonstrate that the blockade of co-stimulatory signals with ICOSmAb in conjunction with CTLA4-1g has a favorable effect to restrain the rejection of corneal transplantation.