非清髓单倍体相合骨髓移植后自然杀伤细胞参与急性移植物抗宿主病的免疫病理学研究  

Immunopathology of NK cells participating in aGVHD after nonmyeloablative haploidentical bone marrow stem cell transplantation

作　　者：雷英英[1,2] 段连宁[1] 罗渊[1] 郭广进[1] 许鹏飞[1] 陆承荣[1] 王喆[1] 向培德[1] 

机构地区：[1]空军总医院中心实验室,北京100142 [2]河北北方学院研究生部,河北张家口075000

出　　处：《解放军医学院学报》2014年第7期725-729,共5页Academic Journal of Chinese PLA Medical School

基　　金：国家自然科学基金项目(30873014)~~

摘　　要：目的研究自然杀伤(natural killer,NK)细胞在非清髓单倍体相合骨髓移植中参与急性移植物抗宿主病(acute graft vs host disease,aGVHD)过程的免疫病理。方法本实验建立了以C57BL/6小鼠为供鼠、CB6F1小鼠为受鼠的急性移植物抗宿主病模型。观察小鼠发生aGVHD的症状体征,流式细胞术检测小鼠移植后嵌合率及NK细胞活化受体NKp46表达强度,免疫荧光染色观察aGVHD靶器官部位NK细胞分布。结果移植鼠aGVHD发生率80%,移植+15 d达到完全嵌合,移植+25 d左右小鼠出现体质量减轻、耸毛、弓背等典型aGVHD症状。发生aGVHD小鼠外周血NK细胞NKp46表达强度低于未发生aGVHD小鼠,受鼠肝汇管区有供鼠源NK细胞浸润。结论在非清髓单倍体相合骨髓移植中NK细胞参与了肝处移植物抗宿主病的病理反应,NK细胞活化受体NKp46表达强弱与aGVHD的发生相关,NKp46表达强度可能为aGVHD诊断提供依据。Objective To study the immunopathology of NK cells participating in aGVHD after nonmyeloablative haploidentical bone marrow stem cell transplantation. Methods A mouse aGVHD model was established with C57BL/6 mice as its donor and CB6F1 mice as its receptor. Symptoms and signs of aGVHD were observed, chimerism and NKp46 expression were detected. Distribution of NK cells in aGVHD target organs was detected with immunofluorescence staining. Results The incidence rate of aGVHD was 80%. The chimerism was achieved in 100% receptors 15 days after transplantation. The body weight of mice was reduced and the symptoms of aGVHD mice such as fur and hunched posture developed about 25 days after transplantation. The expression level of NKp46 was lower in aGVHD mice than in aGVHD-free mice. NK cells infiltrated from donors into the portal area of receptors. Conclusion NK cells participate in the pathological response of liver graft versus host disease during nonmyeloablative haploidentical bone marrow stem cell transplantation. NKp46 expression is associated with aGVHD, thus providing evidence for the diagnosis of aGVHD.

关 键 词：非清髓单倍体相合骨髓移植 急性移植物抗宿主病 自然杀伤细胞 NKp46 

分 类 号：R457.7[医药卫生—治疗学]