Abstract
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 CD56bri NK cells led to a decreased ratio of CD56dim and CD56bri 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 CD56dim and CD56bri NK cells as well as decreased NK1 populations in both PB and BM.
Highlights
Xing-Xing Yu and Ting-Ting Han contribute to this paper Precis: granulocyte colony-stimulating factor (G-CSF) treatment decreased the IFN-c-secreting Natural killer (NK) population (NK1) dramatically in bone marrow (BM) and peripheral blood (PB), but increased the IL-13-secreting NK, TGF-b-secreting NK and IL-10-secreting NK populations significantly in BM.Allogeneic haematopoietic stem cell transplantation remains one of the most important curative methods for malignant haematologic diseases
The following main findings were made: 1) in vivo application of G-CSF decreased the percentage of NK cells and modulated NK subpopulations, leading to an increased ratio of CD56bri to CD56dim subsets and low levels of NK1 cells, and 2) a high dose of NK1 cells infused into allografts correlated with the development of chronic graft-vs-host disease (GVHD) after transplantation
The in vivo application of G-CSF led to expansion of NK2/NK3/NKr cells in G-CSF-primed bone marrow (GBM) compared to those in NGBM and GPB; roles of NK2/NK3/ NKr cells in allografts and clinical outcome post-transplantation were still unclear
Summary
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the most important curative methods for malignant haematologic diseases. Previous studies have shown that donor and recipient KIR ligand mismatch can initiate donor NK cell alloreactivity, leading to decreased leukaemia relapse and decreased GVHD incidence post-haploidentical transplantation with T cell depletion in vitro.[5] the predictive value of KIR ligand mismatch on clinical outcome has been inconsistent among different transplantation centres utilizing different protocols.[6,7] One of the most important reasons would be the in vivo application of G-CSF for donor stem cell preparation that decreased the cytotoxicity of NK cells.[8,9] previous studies have considered only the cytotoxic roles of NK cells under haploidentical transplantation while neglecting the immune regulatory effect of NK cells
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