阻断OX40和CD40协同共刺激信号延长小鼠胰岛移植物存活时间  

Mice islet aliograft tolerance induced by blockade of OX40/OX40L and CD40/CD154 costimulation pathway

作　　者：陈恕求[1] 陈明[1] 许斌[1] 任全[1] 王奕铎[1] 王旭辉[1] 李宪昌[2] 

机构地区：[1]东南大学医学院东南大学附属中大医院泌尿外科,南京210009 [2]哈佛大学医学院BID医学中心附属移植研究中心

出　　处：《中华器官移植杂志》2012年第3期174-177,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（81070592）;江苏省自然科学基金项目（BK2009275）

摘　　要：目的研究阻断OX40／OX40L和CI）40／CD154L协同共刺激通路对小鼠胰岛移植物存活的影响及其机制。方法以DBA／2小鼠为供者，C57BL／6小鼠为受者，制作胰岛移植模型。受鼠分为4组。（1）对照组，注射IgG；（2）抗OX40组，注射抗OX40L单克隆抗体；（3）抗CD154组，注射抗CD154单克隆抗体；（4）联合治疗组，注射抗OX40L单克隆抗体和抗CD154单克隆抗体。记录各组胰岛移植物平均存活时间（MST）。将CD154敲除小鼠处死，取其脾脏T淋巴细胞，体外检测活化T淋巴细胞表面OX40的表达；在活化T淋巴细胞中加入不同浓度的抗OX40L单克隆抗体，体外检测T淋巴细胞增殖情况。结果对照组胰岛移植物MST为19d，抗CD154组胰岛移植物MST为48d（P〈0．05）；抗OX40组胰岛移植物MST为22d，与前两组相比较，差异无统计学意义（P〉0．05）；联合治疗组胰岛移植物MST〉150d，高于另外3组（P〈0．05）。66％的胞表达OX40，较初始T淋巴细胞的表达率高（2％，P〈0．05）；加入抗OX40L单克隆抗体后，T淋巴细胞增殖受抑制且呈剂量依赖性。结论阻断OX40／OX40L和CD4{}／CD154L双通路可诱导小鼠胰岛移植物长期存活，其发挥作用的关键机制是抑制了T淋巴细胞的增殖。Objective To investigate the effects of blockade of OX40/OX40I. costimulation pathway on mice islet allograft tolerance in CD40/CD154 costimulation pathway blockade mice. Methods C57BL/6 mice were induced into diabetes mellitus as recipients, and were transplanted with DBA/2 mice islets. The recipients were divided into four groups, （1） treated with IgG as controls, （2） anti OX40L mAb, （3） anti-CD154, （4） combined treatment of anti-OX40L mAb and anti-CD154 mAb. The mean survival time （MST） of islet allograft was observed. The expression of OX40 in activated T cells of CD154 deficient mice was detected. Effector T cells were obtained from the spleen of CD154 deficient mice cultured with or without anti-OX40L mAb for 3 days. The proliferation of T cells was assayed. Results The MST in the control group, anti-OX40L mAb group, anti-CD154 mAb group and anti-OX40L mAb ＋ anti-CD154 mAb group was 19, 22, 48, and 〉150 days respectively （P〈0. 05）. The OX40 expression was readily induced in the 66% activated T effector cells. CD154 deficient T effeetor cells proliferation was inhibited by the addition of anti-OX40L mAb in the culture in a dose-dependent fashion. Conclusion The blockade of OX40/OX40L costimulation pathway can promote islet allograft tolerance in CD40/CD154 costimulation pathway blockade mice by inhibiting the proliferation of T cells.

关 键 词：小鼠 胰岛移植 抗原 OX40 抗原 CD40 移植物存活 

分 类 号：R657.5[医药卫生—外科学]