摘要
目的评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为异基因造血干细胞移植的临床应用提供科学依据。方法经过致死剂量照射的BALB/C小鼠接受异基因C57BL/6小鼠骨髓移植。根据回输的细胞不同分为4组:1)B6 CCR5 KO组,受者接受C57BL/6 CCR5-/-小鼠骨髓和脾脏细胞;2)B6 WT组,受者接受野生型C57BL/6小鼠骨髓和脾脏细胞;3)B6 CCR5 KO BMC组,受者只接受C57BL/6 CCR5-/-小鼠骨髓细胞;4)B6 WT BMC组,受者只接受野生型C57BL/6小鼠骨髓细胞。结果与B6 WT组比较,B6 CCR5 KO组小鼠以更快的速度死于急性移植物抗宿主疾病(GVHD);其受者体内的CD8+T细胞大量增生;T细胞恢复后产生更多的干扰素-γ(INF-γ)和肿瘤坏死因子-α(TNF-α),T细胞有丝分裂原刀豆素水平处于较高水平,进一步促进T细胞增生。组织学检测提示移植剔除CCR5基因受者细胞的小鼠肾脏出现病理损伤,肝脏存在更为严重的病理变化。结论剔除CCR5基因的异基因骨髓移植使GVHD发病率增加,供者CD8+T细胞在受者体内增生加重肝肾损害。提示CCR5在异基因骨髓移植中起着重要作用。
Objective To evaluate the role of gene CCR5 on donor cells in models where intensive preconditioning of the recipient occurs, thus provide the scientific evidence for clinical experience of allo-HSCT. Methods Lethally irradiated BALB/C mice received C57BL/6 mice is allogeneic bone marrow transplants. We divided mice into 4 groups according to receiving variant donor cells： B6 CCR5 KO group, receiving C57BL/6 CCR5^-/- mice bone marrow cells and splenocytes; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells and splenocytes; B6 CCR5 KO BMC group, receiving C57BL/6 CCR5^-/- bone marrow cells alone; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells alone. Results Compared to B6 WT group, B6 CCR5 KO group succumbed to acute GVHD at an accelerated rate. Donor CD8^＋ T cells expanded to a significantly greater extent in recipients of CCR5 KO vs WT control cells. T cells recovered from recipients of CCR5 KO cells roduced more IFN-γ and TNF- Aand proliferated to a T-cell mitogen at a significantly greater level than T cells from recipients of WT cells, indicating that CCR5 plays a role in downregualting donor alloreative CD8^＋ T-cells expansion. Histological assessment of the mice indicated pathological lesions in the kidney and a greater degree of liver pathological changes in mice that received CCR5 KO donor grafts. Conclusion The absence of gene CCR5 on donor cells results in increased GVHD and donor CD8^＋ T cells as well as hepatic and renal lesions in allo-HSCT, which indicated gene CCR5 is very important in allo-BMT.
出处
《首都医科大学学报》
CAS
2006年第4期488-491,共4页
Journal of Capital Medical University
