摘要
目的探讨供体特异性输注(donor specific transfusion,DST)细胞上CD47的表达在诱导同种异体小鼠心脏移植免疫耐受中的作用机制。方法实验动物随机分为3组,3组均以C57BL/6(CD47+/+)小鼠为供者,具体分为:(1)non-DST组:以未行CD47+/+DST及CD47-/-DST的BALB/c小鼠为受者。(2)CD47-/-组:以输注CD47-/-DST的BALB/c小鼠为受者。(3)CD47+/+组:以输注CD47+/+DST的BALB/c小鼠为受者。于术前7d、5d、3d分别接受共刺激因子封闭。观察心脏移植物存活时间;用流式细胞技术检测受体脾脏内的树突状细胞的激活情况;用体外混合淋巴细胞试验检测供体抗原特异性T淋巴细胞的增殖情况;排斥反应时及移植后150d行移植心病理切片检查。结果与non-DST组比较(移植心中位生存时间为7d),CD47-/-组移植心中位存活时间较长(中位生存时间为42d),但其存活时间明显短于CD47+/+组(中位存活时间>150d,P<0.01)。与CD47+/+组比较,CD47-/-组受鼠脾脏内表达CD11c+CD86+、CD11c+I-Adhi树突状细胞的百分比明显增加(P<0.01,P<0.05)。CD47-/-DST7d后,受鼠的供体反应性T淋巴细胞增殖明显增加,而CD47+/+组的供体反应性T淋巴细胞增殖明显受抑制(P<0.01)。CD47-/-组移植心受排斥时,心肌组织内可见大量单个核细胞浸润,而CD47+/+组移植心术后150d时仍未见明显单个核细胞浸润,且与正常对照的心脏无明显差别。结论 DST细胞上CD47可以通过抑制受体树突状细胞激活及抑制供体抗原特异性T淋巴细胞反应的途径诱导免疫耐受。
Objective To investigate the function of cluster of differentiation antigen（CD）47 expressed on donor specific transfusion（DST）cells in immunotolerance induction of mouse heart transplantation.Methods Mouse abdominal heterotopic heart transplantation model was established by using BALB/c mice as recipients and C57BL/6 mice as donor,respectively.BALB/c recipients received DST from CD47＋/＋（CD47 wild type,CD47＋/＋ group）or CD47-/-（CD47 gene knock-out,CD47-/-group）donors on day 7 and anti-CD154 mAb on day 7,5 and 3 before transplantation.Heart grafts survival time was observed.Host dendritic cell（DC）activation was assessed by flow cytometry and anti-donor T cell responses were assessed by in vitro mixed lymphocyte reaction（MLR）.Heart grafts hematoxylin-eosin（HE）staining was performed on reject reaction and day 150 after transplantation.Results The longest survival time of graft was observed in CD47＋/＋DST group（mean survival time 150 d）,which was significantly longer than non-DST group（mean survival time =7 d）and CD47-/-DST group（mean survival time =42 d）.The percentages of splenic CD11c＋CD86＋ and CD11c＋I-Adhi were increased significantly in CD47-/-DST-treated mice with significantly stronger anti-donor MLR.Obvious monocytes infiltration was observed in cardiac muscle tissues in CD47-/-group while less monocytes infiltration was observed in CD47＋/＋ group.Conclusion CD47 expressed on DST cells plays an important role in DST-induced immunotolerance,presumably inhibiting recipient DC activation and inhibiting anti donor T cell response.
出处
《器官移植》
CAS
2010年第6期372-376,共5页
Organ Transplantation
基金
吉林省科技厅科技计划发展项目(20070729-16)
关键词
心脏移植
分化群47
供体特异性输注
免疫耐受
信号调节蛋白α
树突状细胞
Heart transplantation
Cluster of differentiation antigen 47
Donor specific transfusion
Immunotolerance
Signal regulatory protein
Dendritic cell
