Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Beijing, China.
J Cell Mol Med. 2018 Jun;22(6):3025-3034. doi: 10.1111/jcmm.13539. Epub 2018 Mar 25.
Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor-derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post-allo-HSCT. The aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post-G-CSF in vivo application. Relative expansion of CD56 NK cells led to a decreased ratio of CD56 and CD56 NK subsets in BM and PB post-G-CSF in vivo application. The expression of CD62L, CD54, CD94, NKP30 and CXCR4 on NK cells was significantly increased in PB after G-CSF treatment. G-CSF treatment decreased the IFN-γ-secreting NK population (NK1) dramatically in BM and PB, but increased the IL-13-secreting NK (NK2), TGF-β-secreting NK (NK3) and IL-10-secreting NK (NKr) populations significantly in BM. Clinical data demonstrated that higher doses of NK1 infused into the allograft correlated with an increased incidence of chronic graft-vs-host disease post-transplantation. Taken together, our results show that the in vivo application of G-CSF can modulate NK subpopulations, leading to an increased ratio of T and NK cells and decreased ratio of CD56 and CD56 NK cells as well as decreased NK1 populations in both PB and BM.
粒细胞集落刺激因子(G-CSF)已广泛应用于异基因造血干细胞移植(allo-HSCT)领域,通过刺激供体骨髓(BM)中的干细胞进入外周血(PB),以便更方便地采集干细胞。供体来源的自然杀伤(NK)细胞在 allo-HSCT 后具有重要的抗肿瘤功能和免疫调节作用。本研究旨在评估 G-CSF 对供者 BM 和 PB 中 NK 细胞的影响。结果显示,G-CSF 体内应用后,BM 和 PB 中核细胞和淋巴细胞中 NK 细胞的比例显著下降,导致 T 细胞和 NK 细胞的比例增加。CD56+NK 细胞的相对扩增导致 BM 和 PB 中 CD56+和 CD56-NK 亚群的比例降低。G-CSF 处理后,PB 中 NK 细胞上 CD62L、CD54、CD94、NKP30 和 CXCR4 的表达显著增加。G-CSF 处理后,BM 和 PB 中 IFN-γ 分泌 NK 细胞(NK1)显著减少,但显著增加了 IL-13 分泌 NK(NK2)、TGF-β 分泌 NK(NK3)和 IL-10 分泌 NK(NKr)。临床数据表明,移植后输注到同种异体移植物中的较高剂量 NK1 与慢性移植物抗宿主病的发生率增加相关。总之,我们的研究结果表明,G-CSF 的体内应用可以调节 NK 亚群,导致 PB 和 BM 中 T 细胞和 NK 细胞的比例增加,CD56+和 CD56-NK 细胞的比例降低,以及 NK1 细胞数量减少。