CAJ | 학술논문

目的研究阻断OX40/OX40L和CD40/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CD1 54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19 d,抗CD154组胰岛移植物MST为48 d(P＜0.05)；抗OX40组胰岛移植物MST为22 d,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＞ 150 d,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CD40/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.
목적 연구조단OX40/OX40L화CD40/CD154L협동공자격통로대소서이도이식물존활적영향급기궤제.방법 이DBA/2소서위공자,C57BL/6소서위수자,제작이도이식모형.수서분위4조.(1)대조조,주사IgG; (2)항OX40조,주사항OX40L단극륭항체；(3)항CD154조,주사항CD154단극륭항체；(4)연합치료조,주사항OX40L단극륭항체화항CD1 54단극륭항체.기록각조이도이식물평균존활시간(MST).장CD154고제소서처사,취기비장T림파세포,체외검측활화T림파세포표면OX40적표체；재활화T림파세포중가입불동농도적항OX40L단극륭항체,체외검측T림파세포증식정황.결과 대조조이도이식물MST위19 d,항CD154조이도이식물MST위48 d(P＜0.05)；항OX40조이도이식물MST위22 d,여전량조상비교,차이무통계학의의(P＞0.05)；연합치료조이도이식물MST＞ 150 d,고우령외3조(P＜0.05).66％적포표체OX40,교초시T림파세포적표체솔고(2％,P＜0.05)；가입항OX40L단극륭항체후,T림파세포증식수억제차정제량의뢰성.결론 조단OX40/OX40L화CD40/CD154L쌍통로가유도소서이도이식물장기존활, 기발휘작용적관건궤제시억제료T림파세포적증식.
Objective To investigate the effects of blockade of OX40/OX40L 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 CD154mAb.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 effector 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.