【摘要】 目的在小鼠同种异体胰岛移植模型上,通过联合阻断CD28和可诱导共刺激分子(ICOS),观察CTLA-4Ig及ICOS单克隆抗体(ICOSmAb)对胰岛移植物功能的影响。方法将小鼠随机分成4组,每组10只。联合阻断组:分别于移植后0、2、4 d和1、3、5 d腹腔内注射CTLA-4Ig 50μg/ kg和ICOSmAb 100μg/kg体重组。ICOS组:移植后1、3、5 d腹腔内注射ICOSmAb 100μg/kg体重组。CTLA4组:移植后0、2,4d腹腔内注射CTLA-4Ig 50μg/kg体重组。对照组:单纯胰岛移植,不做CT- LA-4Ig和ICOSmAb处理组。观察术后移植物存活时间和病理改变,RT-PCR检测移植组织中IL-2、IL-10mRNA表达,流式细胞仪检测CD4~+、CD8~+T淋巴细胞表达。结果联合阻断组小鼠移植物存活时间平均为(31.00±6.57)d,较其他3组延长,差异有统计学意义(P<0.05);IL-2和IL-10 mRNA表达水平分别为(44.23±6.24)和(65.23±11.02),与其他3组比较,IL-2 mRNA表达差异有统计学意义(P<0.05),而IL-10mRNA表达差异无统计学意义(P>0.05);CD4~+、CD8~+T淋巴细胞荧光阳性百分率分别为(13.73±0.49)%和(14.56±0.31)%,表达上调均不明显;移植胰岛光镜检查接近正常。结论应用CTLA-4Ig和ICOSmAb联合阻断CD28和ICOS,可以明显抑制胰岛移植物排斥反应。更多还原

【Abstract】 Objective To study the effects of costimulatory blockade with anti-inducible costimula- tor antibody in conjunction with CTLA4Ig on preventiun of islet allograft rejection.Methods Experimental animals were divided into 4 groups in random,10 rats in each group:The CTLA4Ig and ICOS mAb-treated group:intraperitoneal injection of CTLA4Ig 50μg/kg on day 0,2,4 and ICOS mAb 100μg/kg on day 1,3 and 5 after islet transplantation;The ICOS mAb-treated group:intraperitoneal injection of ICOS mAb 100μg/kg on day 1,3 and 5 after islet transplantation;The CTLA4Ig-treated group:intraperitoneal injection of CTLA4Ig 50μg/kg on day 0,2 and 4 after islet transplantation;Control group:simple islet transplantation, not subject to CTLA4Ig and ICOS mAb.HE stain for kidney was used to evaluate the histology,and immuno- histochemical stain of insubn-Ab used to determine the expression of insulin.The expression of CD4~+ and CD8~+ T cells was detected by flow cytometry.The expression of IL-2 and IL-10 mRNA was detected by RT- PCR.Results The mean survival time in CTLA4Ig and ICOS mAb-treated group was(31.00±6.57) days,which was significanntly different from that in other three groups(P<0.05).The expression level of IL-2 mRNA in CTLA4Ig and ICOS mAb-treated group was(44.23±6.24),which was obviously different from other three groups(P<0.05),but there was no significant difference in the expression level of IL-10 mRNA between among the groups(P>0.05).The number of CD4~+ and CD8~+ T cells in CTLA4Ig and ICOS mAb-treated group was(13.73±0.49)% and(14.56±0.31)% respectively,showing no obvious up-regulation on the day 21 after transplantation.Uner light microscopy,the morphology of islets was close to the normal.Conclusion The blockade of costimulatory signals with ICOS mAb in conjunction with CT- LA4Ig has a favorable effect to restrain the rejection of islet transplantation.更多还原