CAJ | 학술논문

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OX40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淋巴细胞间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125 d,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.
목적 관찰억제기억성T림파세포공자격분자OX40연장이도이식소서존활시간적작용,탐토기작용궤제.방법 채용면역자주법제비초시성、류기억성급기억성CD8+T림파세포,병채용역전록취합매련반응법검측3충T림파세포상OX40적표체량.장C57BL/6소서비장T림파세포경미정맥주사급Rag-/-소서.장Rag-/-소서분위3조,대조조:급여동형IgG;치료조:급여항OX40L단극륭항체;기인고제조:수주적T림파세포유OX40기인고제적C57BL/6소서공급.T림파세포수주6주후,사용련뇨매소유도건립당뇨병모형,연후이DBA/2소서위공자,진행이도이식,이식후관찰화비교3조간이도이식물적존활시간.결과 OX40재초시성、류기억성화기억성T림파세포상적상대표체량분별위2.87、111.24화146.15,류기억성화기억성T림파세포간OX40표체량적차이무통계학의의(P＞0.05),단균현저고우초시성T림파세포(P＜0.01).대조조、치료조화기인고제조이도이식물적존활시간분별위21、130화125 d,치료조화기인고제조간이도이식물존활시간적차이무통계학의의(P＞0.05),이자균현저장우대조조(P＜0.05).결론 OX40재기억성T림파세포표면고표체,차조단OX40공자격분자통도가명현연장이도이식물적존활시간,억제OX40/OX40L공자격통도가능시유도이도이식면역내수적관건점지일.
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 cells 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 B6 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 knock-out 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.