NK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

本研究探讨自然杀伤（NK）细胞在小鼠异基因骨髓移植（allo—BMT）中对移植排斥、造血及免疫重建的影响。以C57BL／6（H-2^b）小鼠为供鼠、BALB／c（H-2^d）小鼠为受鼠，分别在致死剂量和非致死剂量（≤7．0Gy）全身照射（TBI）的预处理条件下进行allo—BMT，移植同时输注供鼠外周T细胞和（或）NK细胞，移植后不同时间检测受鼠外周血白细胞、骨髓CD34^＋细胞数和外周血淋巴细胞中CD3^＋细胞、CD19^＋细胞及供鼠来源的H-2K^b＋细胞表达的百分率，并对不同移植组的存活率、植入与排斥、造血及免疫重建进行比较。结果表明：在致死剂量TBI预处理的移植中，输注NK细胞与不输注NK细胞的移植组比较，存活率显著增高（60天存活率为70％vs 0．0％）；白细胞数、CD19^＋细胞表达及骨髓CD34^＋细胞数恢复快；H-2K^b＋细胞的表达水平高（86．68±4．45）％vs（4．68±0．32）％]。移植后28天输注NK细胞组CD3^＋细胞表达水平明显低于不输注NK细胞组（33．69±3．36）％们（50．40±5．06）％，P〈0．01]，移植后60天两组比较差异无显著性（P〉0．05）。在非致死剂量TBI预处理的移植中，移植后30天．异基因骨髓移植组H-2K^b＋细胞表达率明显下降，移植后60天已下降至移植前水平；而输注高浓度和低浓度NK细胞的两组在移植后60天仍能检测到80％以上的H-2^b＋细胞表达。结论：在小鼠allo—BMT中，同种异基因反应性NK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。

Effects of Natural Killer Cells on Engraftment and Reconstitution of Hematopoiesis and Immunity in Mice Undergoing Allogeneic Bone Marrow Transplantation

The aim of this study was explore the effect of natural killer (NK) cells on engraftment and reconstitution of hematopoiesis and immunity in mice undergoing allogeneic bone marrow transplantation (allo-BMT). Lethally and nonlethally irradiated BALB/c (H-2(d)) mice were transplanted with C57BL/6 (H-2(b)) bone marrow plus donor peripheral T cells and/or NK cells. Recipient CD34(+), H-2K(b+), CD3(+) and CD19(+) cells were detected by flow cytometry; peripheral blood leukocytes were counted by auto-cytometry; survival rates, engraftment, hematopoietic and immune recovery of recipients in different transplant groups were then observed. The results indicated that as 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 (survival rates at 60 days were 70% and 0.0% respectively); leukocyte count, expression level of CD19(+) cell and CD34(+) cell count recovered rapidly; expression level of H-2K(b+) cells obviously increased (86.68 +/- 4.45)% vs (4.68 +/- 0.32)%]; expression level of CD3(+) cell at day 28 after transplantation obviously decreased (33.69 +/- 3.36)% vs (50.40 +/- 5.06)%, p < 0.01], at day 60 there was not significant difference between the 2 groups (p > 0.05). In nonlethally irradiated and allo-BMT group without NK cell infusion, the expression level of H-2K(b+) at day 30 after transplantation significantly decreased, and reduced to level before transplantation at day 60; while expression of H-2K(b+) yet could be detected with > 80% at day 60 after transplantation in group infused with high and low concentration of NK cells. It is concluded that in allo-BMT mice, alloreactive NK cell inhibits graft rejection, enhances engraftment, promotes the reconstitution of hematopoiesis and immunity, and increases survival rates.