联合阻断CD28和ICOS对移植胰岛功能影响的实验研究

目的:探讨CTLA-4Ig及可溶性B7RP-1融合蛋白联合阻断CD28和ICOS对移植胰岛功能的影响。方法:在异种胰岛移植模型的基础上48只实验动物随机分成4组,每组12只,供体为SD大鼠,受体为近交系昆明小鼠。联合处理组(A组):分别于移植后0、2、4d和1、3、5d腹腔内注射CTLA-4Ig和可溶性B7RP-1融合蛋白组;可溶性B7RP-1融合蛋白处理组(B组):移植后1、3、5d腹腔内注射可溶性B7RP-1融合蛋白组;CTLA-4Ig处理组(C组):移植后0、2、4d腹腔内注射CTLA-4Ig组;对照组(D组):单纯胰岛移植,不做CTLA-4Ig和可溶性B7RP-1融合蛋白处理组。通过观察大鼠胰岛移植后移植物存活时间和移植胰岛病理改变,并用RT-PCR方法检测IL-2和IL-10在移植组织中的表达情况。结果:联合处理组大鼠移植胰岛存活时间较对照组及CTLA-4Ig处理组和可溶性B7RP-1融合蛋白组明显延长,移植胰岛光镜检查接近正常,IL-2mRNA表达差异有显著性[(42.55±6.34)%VS(112.55±15.34)%,P<0.01],IL-10mRNA表达差异无显著性[(105.35±15.16)%VS(102.23±16.02)%,P>0.05]。结论:应用CTLA-4Ig+可溶性B7RP-1融合蛋白联合阻断CD28和ICOS,可以明显的抑制排斥反应,提高移植物的存活率。

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

Objective:To study the effects of costimulatory blockade with anti-inducible costimulator antibody in conjunction with CTLA4Ig on prevention of islet xenograft rejection .Methods:Islets were transplanted into the liver of streptozotocin (150mg/kg) induced diabetic mice. Experimental animals were divided into four groups in random ,12 rats for each group. The group of CTLA4Ig and anti-icos antibody(B7RP-1) (A guoup): intraperitoneal injection with CTLA4Ig on day 0. 2. 4 and anti-icos antibody on day 1. 3. 5 after islet transplantation; the group of anti-icos antibody(B guoup): intraperitoneal injection with anti-icos antibody on day 1. 3. 5 after islet transplantation;the group of CTLA4Ig(C guoup): intraperitoneal injection with CTLA4Ig on day 0. 2. 4 after islet transplantation ;control group(Dgroup) : simple islet transplantation ,not to inject CTLA4Ig or anti-ICOS antibody .Results:Compared with others ,survival time of A group was obviously prolonged, islet shape was near to nomal under light microscope, and IL-2mRNA expression was obvious different. [(42.55±6.34)%VS(112.55±15.34)%,P<0.01],but IL-10mRNA expression showed not difference [(105.35±15.16)%VS(102.23±16.02)%,P>0.05]. Conclusion:These findings demonstrate that the blockade of costimulatorysignals with anti-ICOS antibody in conjunction with CTLA4Ig has a favorable effect to restrain the rejection of islet transplantation.