TCR Vβ亚家族分析法识别小鼠亚临床MHC 缺失诱导的移植物抗宿主病  

Analysis of TCR Vβsubfamily for the diagnosis of MHC deficiency-induced subclinical graft-versus-host disease

作　　者：李晓帆[1] 李乃农[1] 田伟[2] 谢何琳 杨凤娥[1] 陈元仲[1] 

机构地区：[1]福建医科大学附属协和医院血液科,福建省血液病研究所,福建省血液病学重点实验室,福州350000 [2]福建医科大学附属协和医院皮肤科,福州350000 [3]福建医科大学附属协和医院药学部,福州350000

出　　处：《中华微生物学和免疫学杂志》2015年第5期321-327,共7页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金（81270641）;国家自然科学基金青年项目（81200400）;教育部博士点基金（20123518120006）;福建省高校杰出青年科研人才培育计划（JA14130）志谢：感谢美国希望之城Dr.DefuZeng教授提供基因敲除小鼠和技术指导支持.

摘　　要：目的：研究T细胞抗原受体（ TCR） Vβ亚家族分析法用于亚临床主要组织相容性复合体（MHC）缺失相关的移植物抗宿主病（GVHD）的检测。方法 BALB／c小鼠给予9．5 Gy（950 rad）全身放射，放射后回输T细胞去除的C57BL／6或DBA／2骨髓细胞。将小鼠分为两组：WT组：回输来自野生型骨髓细胞106个／只；MHC－／－组：回输来自MHCⅡ类分子缺失的骨髓细胞106个／只。移植后观察小鼠GVHD典型症状，病理切片确诊GVHD。结果典型的MHCⅡ类分子缺失相关的GVHD可以在异基因（H-2b→H-2d）C57BL／6动物模型中诱导。在DBA ／2模型，MHCⅡ类分子缺失诱导的是亚临床的GVHD。 TCR Vβ亚家族分析提示TCR Vβ6与病理符合度好，可识别该模型亚临床GVHD。结论利用TCR Vβ亚家族分析法发现TCR Vβ6升高可作为识别小鼠亚临床MHC缺失诱导的移植物抗宿主病的指标。Objective To analyze the possibility of using TCR Vβsubfamily as the diagnostic in-dicators for major histocompatibility complex（ MHC） deficiency-induced graft-versus-host disease（ GVHD） . Methods The BALB/c mice were given 9.5 Gy （950 rad） of irradiation and transplanted with 106 of T-cell depleted （TCD） bone marrow cells from C57BL/6 and DBA/2 mice with MHC Ⅱ deficiency.Two control groups were set up accordingly by injection of TCD bone marrow cells from wild type （ WT） C57BL/6 and DBA/2 mice.Several parameters including the body weight, the GVHD clinical score and the survival time of the recipients were monitored.Flow cytometry analysis and mixed lymphocyte culture test were performed for the evaluation of autoimmune responses.Histological examination was used to analyze the severity of GVHD.Results The MHC deficiency-induced GVHD was successfully induced in the irradiated BALB/c mice receiving MHC mismatched allogeneic hematopoietic cell transplantation （ allo-HCT ） . The MHC matched DBA/2 mice with MHC deficiency could be used as the mice model of subclinical GVHD.Changes of the TCR Vβ6 were consistent with the results of histopathological examination.Conclusion Highly ex-pressed TCR Vβ6 could be used as indicators for the diagnosis of MHC deficiency-induced subclinical GVHD.

关 键 词：移植物抗宿主病 TCR VΒ亚家族 主要组织相容性复合体 克隆清除 动物模型 

分 类 号：R457.7[医药卫生—治疗学]