抗小鼠CD122抗体促进脐血CD34^＋细胞在NOD/SCID小鼠体内的重建  

Anti-mouse CD122 Antibody Promotes the Hematopoietic Repopulating Capacity of Cord Blood CD34^+ Cells in NOD/SCID Mice

作　　者：盛梦瑶 石慧 邢文 汪文君 司晓慧 白洁 袁卫平 周圆 杨逢春 

机构地区：[1]中国医学科学院、北京协和医学院血液病医院、血液学研究所、实验血液学国家重点实验室,天津300020

出　　处：《中国实验血液学杂志》2014年第6期1673-1677,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(81270575,81170512,81328003);天津市应用基础研究重点项目(13JCZDJC31200)

摘　　要：本研究旨在探讨抗小鼠CD122抗体促进人脐血CD34+造血干细胞在非肥胖糖尿病/重症联合免疫缺陷(NOD/SCID)小鼠体内的重建能力。对NOD/SCID小鼠进行半致死剂量γ射线照射,照射后腹腔注射200μg同型对照抗体或者抗小鼠CD122抗体,6-8 h后经尾静脉注射人脐血CD34+细胞或者注入PBS作为对照。处理后第2、3、4周取仅注射抗小鼠CD122抗体或同型对照抗体的小鼠外周血,动态监测小鼠NK细胞比例变化。在经过脐血CD34+细胞移植的小鼠中,利用流式细胞术对移植后小鼠骨髓中人CD45+比例以及CD45+细胞亚群中人CD34,CD19和CD33比例进行分析,观察抗小鼠CD122抗体对人造血干细胞在小鼠体内重建能力的影响。结果表明,用抗CD122抗体处理后2周和3周时,小鼠外周血中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NOD/SCID小鼠(12.2±1.4)%和(13.3±1.2)%相比下降约60%。在移植了人脐血CD34+细胞的小鼠中,同时用CD122抗体处理组在移植后6周和8周时小鼠骨髓中h CD45+比例分别为(63.0±12.2)%和(53.2±16.3)%,明显高于同型对照抗体组中h CD45+比例(7.7±3.6)%和(6.1±2.4)%。此外,经过抗CD122抗体处理组的小鼠移植8周后骨髓中仍能够明显的检测到人CD34+细胞的存在。结论:抗小鼠CD122抗体通过降低NOD/SCID小鼠的NK细胞的比例,大大促进了人脐血CD34+造血干细胞在免疫缺陷小鼠体内的重建能力。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 γrayNOD /SCID mice were intraperitoneally injected with 200 μmouse 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 antimice CD122 antibody or control antibody alone were sacrificed at different time point（ at week 2and 4 weeks）after the injectionand 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 micephenotype 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 antiCD122 antibody injection respectivelywhich decreased by 60%compared with the mice injected with isotype control antibody.After 6 and 8 weeks of cord blood CD34^＋ cell transplantationthe 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）%respectivelywhich were dramatically higher than that in the mice treated with isotype control antibody（ 7.7 ± 3.6）%and（ 6.1 ± 2.4）%.Moreoverat 8 weeks after transplantationhuman 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.

关 键 词：造血干细胞 NK细胞 造血重建 NOD/SCID小鼠 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R331.2[医药卫生—基础医学]