Effect of the in vivo application of granulocyte colony‐stimulating factor on <scp>NK</scp> cells in bone marrow and peripheral blood

Yu, Xingxing; Han, Tingting; Xu, Lei; Chang, Ying‐Jun; Huang, Xiao‐Jun

doi:10.1111/jcmm.13539

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…These findings were in opposition to Melve et al (14), who found lower NK cell fractions after G-CSF stimulation despite the fact that no changes in the absolute NK cell concentrations was observed in that study. Within NK cell subtypes, smaller studies found an increase in the immature, cytokine-producing CD56bright and a corresponding decrease of the mature, effector CD56dim subset after G-CSF (14,29). On the contrary, our results indicate preservation of the CD56dim subtype, as the subset distribution was not altered by G-CSF.…”

Section: Discussioncontrasting

confidence: 61%

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

et al. 2021

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. G-CSF is the preferential mobilizing agent in healthy donors for PBSC grafts, yet effects of G-CSF on TCR γδ and NK cells are scarcely uncovered and could influence the graft composition and potency of these cells. Therefore, we analyzed T and NK cell subsets and activation markers in peripheral blood samples of 49 donors before and after G-CSF mobilization and—for a subset of donors—also in the corresponding graft samples using multicolor flowcytometry with staining for CD3, CD4, CD8, TCRαβ, TCRγδ, Vδ1, Vδ2, HLA-DR, CD45RA, CD197, CD45RO, HLA-DR, CD16, CD56, and CD314. We found that TCR γδ cells were mobilized and harvested with an efficiency corresponding that of TCR αβ cells. For TCR γδ as well as for TCR αβ cells, G-CSF preferentially mobilized naïve and terminally differentiated effector (TEMRA) cells over memory cells. In the TCR γδ cell compartment, G-CSF preferentially mobilized cells of the nonVδ2 types and increased the fraction of HLA-DR positive TCR γδ cells. For NK cells, mobilization by G-CSF was increased compared to that of T cells, yet NK cells appeared to be less efficiently harvested than T cells. In the NK cell compartment, G-CSF-stimulation preserved the proportion of CD56dim NK effector cells which have been associated with relapse protection. The expression of the activating receptor NKG2D implied in anti-leukemic responses, was significantly increased in both CD56dim and CD56bright NK cells after G-CSF stimulation. These results indicate differentiated mobilization and altering properties of G-CSF which could improve the effects of donor TCR γδ and NK cells in the processes of graft-versus-leukemia for relapse prevention after HSCT.

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Section: Discussioncontrasting

confidence: 61%

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

et al. 2021

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“…G-CSF plays an important role in regulating immune cell number and function in allografts. Previous study indicated that G-CSF modulated NK subpopulations in PB and BM ( Yu et al, 2018 ). G-CSF limited the IFN-γ signaling in T cells and induce immune tolerance ( Franzke et al, 2003 ; Chang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 97%

Rapamycin Promotes the Expansion of Myeloid Cells by Increasing G-CSF Expression in Mesenchymal Stem Cells

Lan

Gao

et al. 2022

Front. Cell Dev. Biol.

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Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Although rapamycin has been widely used in treating various hematologic diseases, the effects of rapamycin are still not fully understood. Here we found that both oral and intraperitoneal administration of rapamycin led to the expansion of myeloid lineage, while intraperitoneal administration of rapamycin impaired granulocyte differentiation in mice. Rapamycin induced bone marrow mesenchymal stem cells to produce more G-CSF in vitro and in vivo, and promoted the myeloid cells expansion. Our results thus demonstrated that intraperitoneal administration of rapamycin might promote the expansion of myeloid lineage while impair myeloid cell differentiation in vivo.

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“…Interestingly, NK cell frequencies negatively associated with circulatory G-CSF in HIV negative persons. A few studies have described a decrease in the percentage of NK cells of total lymphocytes in the bone marrow and peripheral blood following G-CSF administration amongst healthy haematopoietic stem cell transplantation donors [ 64 , 65 ]. It is possible that a direct link seen on NK cells in previous studies might also be noticed here.…”

Section: Discussionmentioning

confidence: 99%

The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans

et al. 2020

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The Duffy Antigen Receptor for Chemokines (DARC)-null trait, common among persons of African descent and associated with lower absolute neutrophil counts (ANCs), may be linked to increased risk to certain infections including HIV-1 but the underlying causes are poorly understood. We hypothesized that DARC-null-linked neutropenia may negatively impact neutrophil immunoregulatory modulation of other immune cells such as natural killer (NK) and CD8+ T cells leading to altered phenotype, functionality and homeostatic activity of these immune cells. HIV-1 uninfected (n = 20) and HIV-1 chronically infected (n = 19) participants were assessed using multi-parametric flow cytometry to determine NK and CD8+ T cell counts, phenotypic profiles, and cytokine production and degranulation. Annexin V and carboxyfluorescein succinimidyl ester (CFSE) staining were used to examine NK cell survival and NK cell and CD8+ T cell proliferation respectively. Participants were genotyped for the DARC-null polymorphism using allelic discrimination assays and ANCs were measured by full blood count. In HIV uninfected individuals, a reduction of total NK cell counts was noted in the absence of DARC and this correlated with lower ANCs. HIV uninfected DARC-null subjects displayed a less mature NK cell phenotype. However, this did not translate to differences in NK cell activation or effector functionality by DARC state. Whilst HIV-1 infected subjects displayed NK cell profiling that is typical of HIV infection, no differences were noted upon DARC stratification. Similarly, CD8+ T cells from HIV infected individuals displayed phenotypic and functional modulation that is characteristic of HIV infection, but profiling was unaffected by the DARC-null variant irrespective of HIV status. Overall, the data suggests that the DARC-null polymorphism and lower ANCs does not impede downstream cytolytic cell priming and functionality.

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Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Cited by 12 publications

References 42 publications

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

Rapamycin Promotes the Expansion of Myeloid Cells by Increasing G-CSF Expression in Mesenchymal Stem Cells

The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans

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