联合阻断CD28/B7和ICOS对大鼠肝移植免疫耐受的实验研究

The study of costimulatory blockade with anti-inducible costimulator antibody in conjunction with CTLA4Ig on prevention of liver allograft rejection

目的拟在大鼠肝移植模型基础上,通过联合阻断CD28/B7和ICOS,探讨CTLA4-Ig及ICOS-Ig对肝移植免疫耐受的影响。方法实验动物随机分成3组,每组12只,供体为SD大鼠,受体为Wistar大鼠。对照组单纯肝移植,不做任何处理;ICOS-Ig处理组移植后1、3、5天腹腔内注射ICOS-Ig;联合处理组分别于移植后0、2、4天和1、3、5天腹腔内注射CTLA4-Ig和ICOS-Ig。通过观察大鼠移植肝病理改变,并用RT-PCR方法检测IL-2和IL-10在移植肝中的表达情况,探讨联合阻断CD28/B7和ICOS对肝移植免疫耐受影响。结果联合处理组大鼠移植肝存活时间较对照组和ICOS-Ig组明显延长,移植肝光镜检查接近正常。RT-PCR检测见IL-2mRNA、IL-10mRNA在受体肝表达各组均有显著差异(P<0.05)。结论应用CTLA4-Ig+ICOS-Ig联合阻断CD28/B7和ICOS,可以明显的抑制排斥反应,诱导移植肝发生免疫耐受。

Objective： To study the effects of costimulatory blockade with ICOS-Ig in conjunction with CTLA4-Ig on prevention of liver allograft rejection . Methods： Othotopic liver transplantation was performed inWistar rats which received SD liver. Experimental animals were divided into three groups in random , 12 rats for each group. Control group ： simple liver transplantation ,not to inject ICOS-Ig ;the ICOS-Ig： group intraperitoneal injection with ICOS-Ig on the day of 1,3,5 after liver transplantation. The CTLA4-Ig and ICOS-Ig;group intraperitoneal injection with CTLA4-Ig on day 0,2,4 and ICOS-Ig on the day of 1,3,5 after liver transplantation . Results .. Compared with others ,survival time o; A group was obviously prolonged, Pathological character of the allografts was observed through light microscope and the immune rejection was slight in A guoup, and IL-2mRNA , IL-10mRNA expressions were obviously different （ P 〈 0. 05）. Conclusion： These findings demonstrate that the blockade of costimulatory signals with ICOS-Ig in conjunction with CTLA4-Ig has a favorable effect on restraining the rejection of liver transplantation.