共刺激阻断剂细胞毒性T淋巴细胞相关抗原4Ig基因修饰树突状细胞对移植肾存活的影响(英文)  

Influence of dendritic cells modified with costimulatory blocker cytotoxic T lymphocyte associated antigen-4 immunoglobulin on the survival of renal allografts

作　　者：黄赤兵[1] 李健[1] 张艮甫[1] 范明齐[1] 王琦[1] 

机构地区：[1]解放军第三军医大学新桥医院泌尿外科肾移植病房,重庆市400037

出　　处：《中国组织工程研究与临床康复》2008年第31期6161-6164,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:前期的研究表明,通过受体全身注射T细胞活化所需的B7/CD28共刺激信号阻断剂细胞毒性T淋巴细胞相关抗原4Ig可以明显延长大鼠移植肾存活,但所需剂量大、影响范围广、特异性差,可能造成全身性不良反应。目的:为了提高细胞毒性T淋巴细胞相关抗原4Ig治疗的靶向性,采用细胞毒性T淋巴细胞相关抗原4Ig基因对肾移植供、受体树突状细胞进行体外修饰,观察两种树突状细胞单独以及联合应用对移植肾存活的影响。设计、时间及地点:随机对照动物实验,于2003-04/2004-07在解放军全军肾病中心实验室完成。材料:肾移植供体为近交系Brown-Norway(BN)大鼠,受体为近交系Lewis大鼠,Wistar大鼠作为无关淋巴细胞供体。方法:分离培养供、受体大鼠骨髓源性树突状细胞,以细胞毒性T淋巴细胞相关抗原4Ig基因重组腺病毒转染供、受体大鼠骨髓源性树突状细胞。构建大鼠肾移植模型,将单独的供、受体树突状细胞,混合的供、受体树突状细胞于肾移植前24h经股静脉注入受体,以未注射树突状细胞的受体为对照。主要观察指标:①移植肾存活时间。②术后20d应用MTT法检测受体脾细胞对供体及无关抗原刺激反应程度。结果:与对照组比较,受体树突状细胞未能延长移植肾存活,但与供体树突状细胞联合应用时可使移植肾存活时间较单独应用供体树突状细胞时明显延长(P<0.01)。注入供体树突状细胞与混合的供、受体树突状细胞大鼠的脾细胞对供体抗原刺激的反应均明显低于对照组(P<0.01),而对无关抗原刺激的反应与对照组无差异。结论:细胞毒性T淋巴细胞相关抗原4Ig基因修饰的供体树突状细胞可以明显延长大鼠移植肾存活时间,受体树突状细胞无此作用,但两种树突状细胞联合应用可以使移植肾获得更长的存活时间。BACKGROUND： Previous studies showed that donor systemic injection of B7/CD28 costimulatory blocker cytotoxic T lymphocyte associated antigen 4 immunoglobulin （CTLA-4Ig） needed in T cell activation can markedly prolong the survival time of rat renal allografts, which, however, has limitations, such as high dose, extensive influence, poor specificity, systemic adverse reactions. OBJECTIVE： In order to improve the targeting of CTLA-4Ig, we modified the dendritic cells of donors and recipients in vitro with CTLA- 4Ig and observed the influence of two kinds of dendritic cells applied alone or together on the survival of renal allografts in rats. DESIGN, TIME AND SETTING： The randomized controlled animal experiment was performed between April 2003 and July 2004 at Laboratory of Department of Urinary Surgery, Xinqiao Hospital, the Third Military Medical University, Chongqing, China. MATERIALS： Kidney donor： inbred Brown-Norway rats, kidney recipient： inbred Lewis rats, unrelated lymphocyte donor： Wistar rats. METHODS： Bone marrow derived dendritic cells of Lewis and Brown Norway rats were modified with CTLA- 4Ig gene recombinant adenovirus in vitro. Animal models of kidney transplantation were built with Brown Norway rats as donors while Lewis rats as recipients. The modified dendritic cells were injected into Lewis rats through femoral vein 24 hours before kidney transplantation alone （group 1 （n=8）, donor dendritic cells; group 2 （n=8）, recipient dendritic cells） and in combination （group 3 （n=8）, donor and recipient dendritic cells）. While the recipients without injection were used as control （group 4 （n=6））. MAIN OUTCOME MEASURES： Survival time of renal allografts; the reaction degrees of splenocytes to donor and unrelated antigen determined by MTT method on day 20 postoperation. RESULTS： Survival time of renal allografts in group 2 was not prolonged compared with group 4 while the survival time was markedly prolonged in group 3 （P 〈 0.01）. The resp

关 键 词：共刺激阻断剂 树突状细胞 肾移植 细胞毒性T淋巴细胞相关抗原4Ig 

分 类 号：R617[医药卫生—外科学]