肝脏抗原递呈细胞对同种异基因供体凋亡细胞的吞噬作用  

The phagocytosis of apoptotic allogeneic lymphocytes by recipient liver antigen-presenting cells

作　　者：汪艳[1] 高毅[1] 孙尔维[2] 陈忠华 

机构地区：[1]南方医科大学珠江医院普外科,广州510282 [2]南方医科大学珠江医院移植免疫研究所,广州510282 [3]华中科技大学同济医学院同济器官移植研究所国家教育部器官移植实验室

出　　处：《中华肝脏病杂志》2006年第5期370-374,共5页Chinese Journal of Hepatology

基　　金：广东省自然基金重点资助项目(037055);国家自然科学基金资助项目(30571757);国家教育部器官移植重点实验室开放基金(20040001)

摘　　要：目的探讨输注供体凋亡淋巴细胞的转归和体内处置等情况。方法分离供体脾淋巴细胞,对其进行荧光标记和诱导凋亡,经免疫磁珠分离纯化后,以一定数量经尾静脉输注受体内。于不同时间点观察其在不同器官的分布。根据分布情况对相关器官组织对供体凋亡细胞的处理进行研究。结果供体凋亡细胞经静脉输注受体内后主要汇集于肝脏。结合肝脏的特殊生理和免疫学功能特点,以肝脏抗原递呈细胞为着眼点进行观察,发现受体肝脏抗原递呈细胞对供体凋亡细胞有活跃的吞噬作用,但存在差异。对供体脾淋巴凋亡细胞的吞噬作用中,肝窦内皮细胞占主要部分,库普弗细胞次之, 肝脏树突状细胞的比例最小。结论肝脏在供体凋亡细胞预输注诱导器官移植免疫耐受的现象中起了关键作用。肝窦内皮细胞和库普弗细胞是本研究中免疫耐受诱导反应的主要抗原递呈细胞,可以作为进一步免疫机制研究的主要对象。Objective To track the location of the transfused apoptotic allogeneic lymphocytes and asses the process of their accumulation and phagocytosis removal as consequences on allograft tolerance in recipient mice. Methods Donor spleen lymphocytes were labeled by CFSE and induced to apoptosis by dexamethasone incubation. After puriftcation by anti-annexin Vconjugated magnetic beads isolation, apoptotic lymphocytes were transfused into recipient mice through the tail veins. Tissue samples from various organs were taken at various time points to analyze the fates of the apoptotic allogeneic lymphocytes and the phagocytosis of them by organ resident APCs. Results Using fluorescent microscopy and flow cytometry, after the apoptotic cells were recognized and uptaken, the largest amount of labeled cells were accumulated in the livers and disappeared within not more than 12 hours. Recipient liver APCs were highly efficacious in phagocytosis of apoptotic allogeneic lymphocytes; the removal was completed within 15 minutes after incubation. LSEC, KC and LDC all phagocytosized the apoptotic allogeneic lymphocytes but with significantly different rates. Considering the numbers of those cells in a normal liver, it could be calculated that LSEC and KC had greater effects in this activity. Conclusions The liver deserves foremost attention for study of the mechanism of allografts tolerance induced by pre-transfusion of apoptotic donor spleen lymphocytes. LSEC and KC are the main functional APCs to the alloantigens.

关 键 词：细胞凋亡 淋巴细胞 移植耐受 肝 抗原递呈细胞 

分 类 号：R657.3[医药卫生—外科学]