Yang Zhi-Gang, Xiong Dan, Zeng Yao-Ying, Liang Liang, Li Qing-Hua, Wu Guo-Cai
Department of Hematology, Affiliated Hospital, Guangdong Medical College, Zhanjian 524001, Guangdong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Jun;16(3):627-32.
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.
本研究旨在探讨自然杀伤(NK)细胞对接受异基因骨髓移植(allo - BMT)小鼠造血和免疫植入及重建的影响。对BALB/c(H - 2(d))小鼠进行致死性和非致死性照射后,移植C57BL/6(H - 2(b))骨髓加供体外周T细胞和/或NK细胞。通过流式细胞术检测受体CD34(+)、H - 2K(b+)、CD3(+)和CD19(+)细胞;通过自动血细胞计数仪计数外周血白细胞;然后观察不同移植组受体的生存率、植入情况、造血和免疫恢复情况。结果表明,与未输注NK细胞的致死性照射allo - BMT组相比,输注NK细胞的致死性照射allo - BMT组生存率显著提高(60天时生存率分别为70%和0.0%);白细胞计数、CD19(+)细胞表达水平和CD34(+)细胞计数迅速恢复;H - 2K(b+)细胞表达水平明显升高[(86.68±4.45)%对(4.68±0.32)%];移植后28天CD3(+)细胞表达水平明显降低[(33.69±3.36)%对(50.40±5.06)%,p < 0.01];60天时两组无显著差异(p > 0.05)。在未输注NK细胞的非致死性照射allo - BMT组中,移植后30天H - 2K(b+)表达水平显著降低,60天时降至移植前水平;而在输注高、低浓度NK细胞组中,移植后60天仍可检测到H - 2K(b+)表达>80%。结论是,在allo - BMT小鼠中,同种异体反应性NK细胞可抑制移植物排斥反应,增强植入,促进造血和免疫重建,并提高生存率。