抗人CD3单克隆抗体体外对再生障碍性贫血造血恢复的机制研究  

Study of mechanism of effects of anti-human CD3 monoclonal antibody on hematopoietic recovery in aplastic anemia in vitro

作　　者：王迎雪[1] 隋潇徽[2] 张建华[3] 张彩[3] 李丽珍[2] 张锑[2] 郭成山[1] 徐从高[2] 

机构地区：[1]山东大学第二医院血液科,济南250033 [2]山东大学齐鲁医院血液学研究室 [3]山东省医学科学院基础医学研究所

出　　处：《临床血液学杂志》2007年第5期293-296,共4页Journal of Clinical Hematology

摘　　要：目的:探讨抗人CD3单克隆抗体(CD3单抗)治疗再生障碍性贫血(再障)的机制。方法:建立再障患者骨髓单个核细胞(BMMNC)中造血细胞液态及半固体培养体系,加入多种造血生长因子进行扩增,并加入CD3单抗药物干预,以ELISA法测定培养上清中肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素-2(IL-2)3种细胞因子的含量,以流式细胞技术分析扩增前后的细胞表面标志,检测CD34+细胞的比例,并观察粒-巨噬细胞集落(CFU-GM)、红系爆式集落(BFU-E)的形成能力,从而研究CD3单抗对再障BMMNC中造血干/祖细胞体外扩增的影响。结果:加CD3单抗组与未加CD3单抗组相比较:体外液态培养7d时,培养上清中TNF-α、IFN-γ、IL-2细胞因子水平明显降低,CD34+细胞的扩增倍数升高,体外半固体培养10d时CFU-GM、BFU-E的产率增加。结论:CD3单抗可明显抑制T细胞介导的异常免疫激活,改善再障患者骨髓中造血细胞的体外扩增效应。Objective：To investigate the effects of the murine anti-human CD3 monoclonal antibody （CD3MoAb） on the expansion of bone marrow hematopoietic cells from aplastic anemia patients. Method： Bone marrow mononuclear cells（BMMNC） of aplastic anemia patients were cultured and expanded using liquid and semisolid assays established in the present study. BMMNC were cultured with different combination of hematopoietic growth factors and CD3 MoAb. The concentrations of TNF-α,IFN-γand IL-2 in the supernatant were determined by ELISA after cultured in liquid system on day 7. CD34^＋ cells were analyzed by flow cytometry before and after expansion. The yield of CFU-GM or BFU-E were counted after culture in semisolid system on day 10. Result：Both the CD34^＋ cells and the colonies of CFU-GM or BFU-E in CD3 MoAb treated group significantly increased, compared to the control group, while the levels of TNF-α,IFN-γand IL-2 in the supernatant of the CD3 MoAb treated group remarkably decreased. Conclusion These results indicate that CD3 MoAb restrain abnormal T cell-mediated immunity, promote in vitro expansion of bone marrow hematopoitic cells of aplastic anemia patients.

关 键 词：贫血 再生障碍性 骨髓造血细胞 细胞扩增 单克隆抗体 CD3 

分 类 号：R556[医药卫生—血液循环系统疾病]