阻断ICOS抑制兔高危角膜移植排斥反应的实验研究

Blockade of ICOS pathway on prevention of high risk corneal allograft rejection in rabbits

目的建立兔角膜移植高危模型,通过阻断ICOS,探讨ICOSmAb对角膜移植排斥反应的影响。方法将新西兰白兔50只随机分成空白对照组、实验组(植片为浸入含有不同浓度ICOSmAb的中期保存液中):A组(1mg.L-1ICOSmAb),B组(10mg.L-1ICOSmAb),C组(25mg.L-1ICOSmAb),D组(250mg.L-1ICOSmAb),每组10只兔。观察术后受体植片角膜混浊情况和植片病理改变,应用流式细胞仪检测植片CD4+、CD8+T淋巴细胞表达情况。结果实验A、B组的植片有较长的生存时间,各实验组及对照组植片平均存活时间(69±34)d、(75±31)d、(45±18)d、(10±3)d、(26±4)d。CD4+、CD8+T淋巴细胞表达明显降低(P<0.05);A组植片组织病理学检查淋巴细胞浸润较对照组及其他实验组明显减少。结论应用ICOSmAb阻断ICOS,可以明显抑制高危角膜移植排斥反应。

Objective To study the effects of anti-inducible co-stimulator antibody on prevention of rabbits corneal allograft rejection. Methods new Zealand rabbits were divided into five groups at random,10 rabbits for each group,control group and four experimental groups of dealing with ICOSmAb at different dosage：group A（ 1 mg· L^-1 ICOSmAb）,group B（ 10 mg· L^-1 ICOS- mAb） ,group C（25 mg· L^-1 ICOSmAb） ,group D（250mg· L^-1 ICOSmAb. The degree of corneal opacity and the histological changes were evaluated. The expression of CD4^＋ and CD8^＋ T cell were detected by flow cytometry. Results Survival time of experiment groups and control group were （ 69 ± 34 ） days, （ 75 ± 31 ） days, （45 ± 18） days, （ 10 ± 3 ） days, （ 26 ± 4） days,respectively. Group A and group B prolonged more time. The numbers of CD4^＋ and CD8^＋ T cell were obvious down-regulated on the 21st day after transplantation, the number of lymphocyte decreased in group A viewing through histological examination compared with control group and other groups. Conclusion ICOSmAb has a favorable effect to restrain the rejection of corneal transplantation.