肝移植受体免疫耐受的诱导及CD4^＋CD25^＋T细胞的重要作用  

Induction of immune tolerance and the importance of CD4^+CD25^+ regulatory T cells in mice liver transplantation

作　　者：黄华[1] 李红春[1] 潘海斌[1] 朱晓峰[2] 孙强[2] 

机构地区：[1]深圳市第三人民医院肝胆外科,广东省深圳市518020 [2]中山大学第一附属医院脏器移植中心,广东省广州市510080

出　　处：《中国组织工程研究与临床康复》2009年第18期3455-3458,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:解决肝移植排斥反应的惟一方法是诱导免疫耐受,而环孢素A对诱导鼠肝移植免疫耐受及T细胞都存在一定影响,可为各种免疫抑制剂的合理使用提供依据。目的:探讨环孢素A诱导肝移植后免疫耐受的可行性及方法,分析CD4+CD25+调节性T细胞在诱导耐受中的作用。设计、时间及地点:随机分组,动物实验观察,2007-01/2008-04在中山大学医学实验动物中心和深圳市第三人民医院肝病研究所完成。材料:健康LEW大鼠66只,BN大鼠78只,CD4、CD25抗体和Foxp3抗体(克隆号PCH101)由美国eBioscience公司生产,环孢素A针剂由北京诺华制药提供。方法:根据用药情况建立6组肝移植模型:同基因对照组:BN大鼠进行同种异体肝移植,移植后不用药。急性排斥组:LEW大鼠作为供体,BN大鼠作为受体,移植后不用药。环孢素A小、中、大剂量组:LEW大鼠作为供体,BN大鼠作为受体,移植后分别给予环孢素A1.0,1.5,2.0mg/(kg·d),疗程均为5d。环孢素A中剂量延期组:LEW大鼠作为供体,BN大鼠作为受体,移植后给予环孢素A1.5mg/(kg·d),疗程7d。除急性排斥组和环孢素A小剂量组各24只外,其他6只/组。主要观察指标:观察各组大鼠移植后生存时间及外周血变化,并检测急性排斥组和组肝、环孢素A小剂量组脾组织中CD4+CD25+Foxp3+Treg的含量。结果:同基因对照组存活时间>100d,而不发生排斥反应。环孢素A小、中、大剂量组存活时间分别为(51.5±2.4),(53.6±3.6),(23.2±2.1)d,环孢素A中剂量延期组和急性排斥组分别为(57.8±7.2),(20.6±3.2)d,除同基因对照组外,各组间差异均有统计性意义(F=114.82,P<0.01)。各组外周血CD4+CD25+Foxp3+Treg的比例无明显差别及增加(P>0.05)。环孢素A小剂量组肝组织中CD4+CD25+Foxp3+Treg的含量明显增加,且高于急性排斥组(P<0.05)。结论:小剂量环孢素A可以诱导免疫耐受,大剂量环孢素A突然停药会导致加速性排斥。CD4+CD25+Foxp3+Treg能促�BACKGROUND： The only way to settle liver transplantation rejection is to induce immune tolerance. Cyclosporin A （CsA） has effect on induce immune tolerance of liver transplantation and the role of T cells, which can provide a basis for rational use of immunosuppressive agents. OBJECTIVE： To investigate the CsA-induced immune tolerance after liver transplantation, analyze the effect of CD4^＋CD25^＋ regulatory T cells on tolerance induction. DESIGN, TIME AND SETTING： A randomized grouping observation of animals was performed at the Medical Laboratory Animal Center of Sun Yat-sen University and Institute of Liver Disease Research the Third Shenzhen City People＇s Hospital from January 2007 to April 2008. MATERIALS： A total of 66 healthy LEW-class rats, 78 BN rats. The CD4, CD25 and Foxp3 antibody （clone No.PCH101） were provided by the American eBioscience Company, CsA injection was provided by the Beijing Novartis Pharma, METHODS： Based on the drug situation, 6 groups of liver transplantation models were established, including： syngeneic control group： BN rats were receiving liver allo-transplantation without medication. Acute rejection group： LEW rats were served as donor BN rats as recipients, without medication. CsA with low, medium and high-dose groups, LEW rats were served as donor, BN rats as recipients, CsA 1.0, 1.5 and 2.0 mg/（kg ·d） were injected after transplantation, lasted for 5 days. Medium-dose extension group LEW rats were served as donor, BN rats as recipients, received CsA 1.5 mg/（kg · d） for 7 days. MAIN OUTCOME MEASURES： The survival time and the peripheral blood changes, as well as CD4^＋CD25^＋Foxp3^＋ Treg content were measured. RESULTS： The survival time of the syngeneic control group was more than 100 days without reject reaction. The survival time of the CsA with low, medium and high-dose groups were （51.5±2.4）, （53.6±3.6） and （23.2±2.1） days, respectively, and （57.8±7.2）, （20.6±3.2） in the medium-dose extension

关 键 词：肝移植 免疫耐受 CD4+CD25+调节性T细胞 排斥反应 

分 类 号：R617[医药卫生—外科学]