自然杀伤细胞对异基因骨髓移植中移植排斥和造血及免疫重建的影响(英文)

Effects of natural killer cells on graft rejection,hematopoietic and immune reconstitution following allogeneic bone marrow transplantation

背景:近几年,自然杀伤细胞与异基因骨髓移植的关系备受关注。目的:探讨自然杀伤细胞在小鼠异基因骨髓移植中对移植排斥、造血及免疫重建的影响。方法:以C57BL/6(H-2b)小鼠为供鼠、BALB/c(H-2d)小鼠为受鼠,分别在致死剂量和非致死剂量(≤7.0Gy)全身照射的预处理条件下进行异基因骨髓移植,移植同时输注供鼠外周T细胞和(或)自然杀伤细胞。结果与结论:在致死剂量全身照射的移植中,输注自然杀伤细胞与不输注自然杀伤细胞的移植组比较,存活率显著增高;白细胞计数、CD19+细胞表达及骨髓CD34+细胞计数恢复快;H-2Kb+细胞的表达水平高。移植后28d,输注自然杀伤细胞组CD3+细胞表达水平明显低于不输注自然杀伤细胞组,60d两组比较差异无显著性意义(P>0.05)。在非致死剂量全身照射的移植中,移植30d,异基因骨髓组H-2Kb+细胞表达百分率明显下降,60d已下降至移植前水平;而输注高浓度和低浓度自然杀伤细胞的两组在移植后60d仍能检测到80%以上的H-2Kb+细胞表达。提示,在小鼠异基因骨髓移植中,同种异基因反应性自然杀伤细胞可以抑制移植排斥,提高造血干细胞的植入水平,促进造血及免疫重建并增加移植受鼠的生存率。

BACKGROUND：The connection between Natural killer（NK）-cells and allogeneic bone marrow transplantation（allo-BMT） has aroused increasing attention.OBJECTIVE：To explore the effect of NK cells on graft rejection,hematopoietic and immune reconstitution in mouse undergoing allo-BMT.METHODS：Lethally and nonlethally irradiated BALB/c（H-2d） mice were transplanted with C57BL/6（H-2b） bone marrow plus donor peripheral T cells and/or NK cells.RESULTS AND CONCLUSION：Compared with lethally irradiated and allo-BMT group without infusion of NK cells,the survival rate in lethally irradiated and allo-BMT group with infusion of NK cells significantly enhanced;leukocytes count,expression level of CD19＋ and CD34＋ cell count recovered rapidly;expression level of H-2b＋ cell obviously increased.Expression level of CD34＋ cell in the group with infusion of NK cells was obviously lower than that of the group without infusion of NK cells at 28 days after transplantation,but there was no significant difference between the 2 groups at 60 days（P 0.05）.In nonlethally irradiated and allo-BMT group without NK cell infusion,expression level of H-2b＋ cell significantly decreased at 30 days after transplantation,and reduced to before transplantation level at 60 days;while expression of H-2b＋ cell yet could be detected with more than 80% at 60 days after transplantation in group infused with high and low concentration of NK cells.In allo-BMT mice,alloreactive NK cell inhibits graft rejection,enhances engraftment,promotes the reconstitution of hematopoiesis and immunity,and increases survival rates.