Sheng Men-Yao, Shi Hui, Xing Wen, Wang Wen-Jun, Si Xiao-Hui, Bai Jie, Yuan Wei-Ping, Zhou Yuan, Yang Feng-Chun
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scinces & Peking Union Medical College, Tianjin 300020, China.
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scinces & Peking Union Medical College, Tianjin 300020, China. E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Dec;22(6):1673-7. doi: 10.7534/j.issn.1009-2137.2014.06.032.
The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.
本研究旨在探讨抗小鼠CD122抗体对人源化小鼠模型——非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠中脐血CD34⁺细胞造血重建能力的影响。用γ射线进行亚致死剂量照射后,给NOD/SCID小鼠腹腔注射200μg小鼠同型对照抗体或抗小鼠CD122抗体。6至8小时后经尾静脉注射人脐血CD34⁺细胞或磷酸盐缓冲盐水(PBS)。在注射后不同时间点(第2、3和4周)处死单独注射抗小鼠CD122抗体或对照抗体的小鼠组,通过流式细胞术分析外周血中NK细胞的百分比。为评估抗小鼠CD122抗体对受体小鼠中脐血CD34⁺细胞重建能力的影响,在移植后第6周和第8周对骨髓进行表型分析。结果显示,注射抗CD122抗体后第2周和第3周,外周血中NK细胞比例分别为(4.6±0.6)%和(5.7±1.7)%,与注射同型对照抗体的小鼠相比降低了60%。脐血CD34⁺细胞移植6周和8周后,用抗小鼠CD122抗体处理的受体小鼠骨髓中人CD45⁺的百分比分别为(63.0±12.2)%和(53.2±16.3)%,显著高于用同型对照抗体处理的小鼠(7.7±3.6)%和(6.1±2.4)%。此外,移植后8周,用抗CD122抗体处理的受体小鼠中明显出现了人CD34⁺细胞。结论是,抗小鼠CD122抗体通过降低NK细胞比例增强了NOD/SCID小鼠中脐血CD34⁺细胞的造血重建能力。