抑制记忆性T淋巴细胞共刺激分子OX40延长小鼠胰岛移植物的存活时间  

Role of OX40 in mechanisms of memory T cells in islet transplant tolerance

作　　者：陈明[1] 陈恕求[1] 胡向农[1] 张晓文[1] 李宪昌[2] 

机构地区：[1]东南大学附属中大医院,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》2011年第5期305-308,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（SBK200922205）

摘　　要：目的观察抑制记忆性T淋巴细胞共刺激分子OX40延长胰岛移植小鼠存活时间的作用，探讨其作用机制。方法采用免疫磁珠法制备初始性、类记忆性及记忆性CD8＋T淋巴细胞，并采用逆转录聚合酶链反应法检测3种T淋巴细胞上OX40的表达量。将C57BL／6小鼠脾脏T淋巴细胞经尾静脉注射给Rag^-/-小鼠。将Rag^-/-小鼠分为3组，对照组：给予同型IgG；治疗组：给予抗OX40L单克隆抗体；基因敲除组：输注的T淋巴细胞由OX4（）基因敲除的C57BL／6小鼠供给。T淋巴细胞输注6周后，使用链脲霉素诱导建立糖尿病模型，然后以DBA／2小鼠为供者，进行胰岛移植，移植后观察和比较3组间胰岛移植物的存活时间。结果OX40在初始性、类记忆性和记忆性T淋巴细胞上的相对表达量分别为2．87、111．24和146．15，类记忆性和记忆性T淋巴细胞问OX40表达量的差异无统计学意义（P〉0．05），但均显著高于初始性T淋巴细胞（P〈0．01）。对照组、治疗组和基因敲除组胰岛移植物的存活时间分别为21、130和125d，治疗组和基因敲除组间胰岛移植物存活时间的差异无统计学意义（P〉0．05），二者均显著长于对照组（P〈0．05）。结论OX40在记忆性T淋巴细胞表面高表达，且阻断OX40共刺激分子通道可明显延长胰岛移植物的存活时间，抑制OX40／OX40L共刺激通道可能是诱导胰岛移植免疫耐受的关键点之一。Objective To investigate the role of OX40 in the mechanisms of memory T cells in islet transplant tolerance. Methods The expression of OX40 on native, like memory and memory CD8＋ T cells was detected by RT-PCR. Splenic T ceils from B6 mice were injected into Rag-/- mice via the tail vein, and the Rag / mice were divided into three groups （n = 8 each） ： control group, given IgG; treatment group, given anti-OX40L; and OX40 knock-out group, given T cells from OX40 knock-out 136 mice spleen. All recipients were induced into diabetes mellitus model after adoptive transfer. Islet transplantation was performed on all Rag- / mice as recipients. The mean survival time of islet was observed. Results The expression of OX40 in native T cells, like memory T cells and memory T cells was 2. 87, 111.24 and 146. 15 respectively. The expression of OX40 in like memory and memory T cells was higher than in native T cells （P〈0. 05）. Comparison with control group , The mean survival time of the DBA/2 islet allografts in treatment group （130 days） and OX40 knockout group （125 days） was significantly longer than in control group （21 days, P〈0. 05）. Conclusion The OX40 expression is high in memory T cells. The mean survival time of the islet allografts can be prolonged by blocking OX40/OX40L pathway. OX40/OX40L pathway may be the key point of transplant tolerance.

关 键 词：小鼠 胰岛移植 记忆T细胞 OX40 移植耐受 

分 类 号：R657.5[医药卫生—外科学]