联合应用未成熟树突状细胞和CD40L单克隆抗体延长大鼠移植肠存活时间  

Combination of immature dendritic cells and anti-CD40L monoclonal antibody prolong rat intestinal allograft survival

作　　者：王海权[1] 徐皓[1] 肇毅[1] 沈历宗[1] 陈涛[1] 华一兵[1] 吴文溪[1] 

机构地区：[1]南京医科大学第一附属医院胃肠外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2006年第7期516-519,F0004,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省"135"工程重点人才基金

摘　　要：目的:研究供体骨髓来源的未成熟树突状细胞(imDC)联合CD40L单克隆抗体(CD40LmAb)对大鼠移植肠的存活时间的影响。方法:实验动物随机分为3组,每组15对,进行不同预处理后进行小肠移植。A阴性对照组,受体小肠移植术前7天注射生理盐水;B组:小肠移植前7天,每只受体经阴茎背静脉注射供体的未成熟DC,细胞数为2×106个;C组:小肠移植前7天,每只受体经阴茎背静脉注射供体的未成熟DC,细胞数为2×106个。同时腹腔注射CD40LmAb200μg/只。B、C组1周后行大鼠异位节段性小肠移植术。于术后3、5、7天分别处死3只大鼠取材,移植肠、受体脾脏分别采用病理学观察及细胞凋亡检测。同时各组取6只大鼠观察受体的存活时间。结果:A、B、C组大鼠小肠移植后平均存活时间分别为:(7.17±1.47)天(、11±2.61)天(、22.67±7.09)天。统计学分析,C组与A、B组比较,差异均有显著性(P<0.01)。C组移植小肠和脾脏炎性细胞浸润、黏膜结构破坏程度和黏膜细胞的凋亡数目明显低于A,B组(P<0.01)。结论:术前输注供体来源的未成熟DC联合CD40LmAb,可一定程度诱导受体产生免疫耐受,显著延长小肠移植大鼠的存活时间。Objective： To investigate the combined effects of C D40L monoclonal antibody （mAb） with immature dendritic cells on donor-specific immune tolerance in rats undergoing small intestinal transplantation. Methods： The pre-dendritic cell was dissociated from donor marrow,and stimulated with GM-CSF and IL-4 in vitro. After five days culture,the expression of co-stimulation molecular and MHC-Ⅱ was detected. Seven days before transplantation of small intestinal from Wistar donors,2 × 10^6 donor-derived immature DC were infused intravenously into SD recipient rat with or without a concomitant intraperitoneal injection of anti-CD40L mAb. Small bowel transplantation was performed and the survival time of small bowel allografts was observed. Apoptotic death in graft-infiltrating cells and in areas of T-dependent lymphoid tissue was analyzed by terminal deoxynucleotidyhransferase-catalyzed dUTP-digoxigenin nick-end labeling and quantitative spectrofluorometry. Results： The survival time in the groups of control,donor immature DC and donor immature DC ＋anti-CD40L mAb was （7.17 ±1.47）days, （11 ± 2.61）days and （22.67 ± 7.09）days respectively. Statistical analysis showed the survival time of small bowel allografts in donor immature DC ＋anti-CD40L mAb group was significantly different from that in donor immature DC group and control group （P 〈 0.01 ）. The degree of the inflammatory infiltrated cells and intestinal mucosa structural injury of mucosa in immature DC ＋anti-CD40L mAb group were significantly mild compared with immature DC group and control group. Conclusion： The pretreatment with immature donor dendritic ceils plus anti-CD40L mAb can induce immune tolerance and prolonge small bowel allografts survival after transplantation.

关 键 词：CD40L MAB 树突状细胞 小肠移植 

分 类 号：R656.7[医药卫生—外科学]