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联合阻断CD28和ICOS对移植胰岛功能影响的实验研究

The study of costimulatory blockade with anti-inducible costimulator antibody in conjunction with CTLA4Ig on prevention of islet allograft rejection
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摘要 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。 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(BTRP-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-2 mRNA expression was obvious different. E(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 eostimulatorysignals with anti-ICOS antibody in conjunction with CTLA4Ig has a favorable effect to restrain the rejection of islet transplantation.
出处 《陕西医学杂志》 CAS 北大核心 2006年第4期400-403,共4页 Shaanxi Medical Journal
关键词 胰岛/移植胰岛/病理生理学 移植物抗宿主反应 抗原 CD28 @ICOS Islets of langerhans/transplantation Islets of langerhans/physiopathology Gralft vs nost reaction Antigens,CD28 @Icos
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参考文献6

  • 1Smith RM,Mandel TE.Pancreatic islet xenotransplantion:the potential for tolerance induction.Immunol Today,2000 ; 21 (1):42. 被引量:1
  • 2Thomas A,Judge,Aimin Tang,et al.The in vivo mechanism oh action of CTLA4Ig.J Immunolog,1996;156:2294. 被引量:1
  • 3Hutloff A,Dittrich AM,Beier KC,et al.ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28.Nature,1999; 397:263. 被引量:1
  • 4Yoshinaga SK,Whoriskey JS,Khare SD,et al.T-cell co-stimulation through B7RP-1 and ICOS.Nature,1999;402:827. 被引量:1
  • 5Dong C,Jueds AE,Temann UA,et al.ICOS costimulatory receptor is essential or T-cell activation and function.Nature,2001 ;409:102. 被引量:1
  • 6Tafuri A,Shahinian A,Bladt F,et al.ICOS is essential for effective T-helper-cell responses.Nature,2001;409:105. 被引量:1

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