Abstract
Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors. The results from flow cytometric cell quantification were examined by bioinformatics analyses. The G-CSF-induced mobilization of lymphocytes was a non-random process with preferential mobilization of naïve CD4+ and CD8+ T cells together with T cell receptor αβ+ T cells, naïve T regulatory cells, type 1 T regulatory cells, mature and memory B cells, and cytokine-producing NK cells. Analysis of circulating lymphoid cell capacity to release various cytokines (IFNγ, IL10, TGFβ, IL4, IL9, IL17, and IL22) showed preferential mobilization of IL10 releasing CD4+ T cells and CD3-19- cells. During G-CSF treatment, the healthy donors formed two subsets with generally strong and weaker mobilization of immunocompetent cells, respectively; hence the donors differed in their G-CSF responsiveness with regard to mobilization of immunocompetent cells. The different responsiveness was not reflected in the graft levels of various immunocompetent cell subsets. Furthermore, differences in donor G-CSF responsiveness were associated with time until platelet engraftment. Finally, strong G-CSF-induced mobilization of various T cell subsets seemed to increase the risk of recipient acute graft versus host disease, and this was independent of the graft T cell levels. Healthy donors differ in their G-CSF responsiveness and preferential mobilization of immunocompetent cells. This difference seems to influence post-transplant recipient outcomes.
Highlights
Allogeneic hematopoietic stem cell transplantation is increasingly used in the treatment of several diseases, especially hematological malignancies and disorders characterized by severe bone marrow failure [1,2,3,4]
Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors
Strong G-CSF-induced mobilization of various T cell subsets seemed to increase the risk of recipient acute graft versus host disease, and this was independent of the graft T cell levels
Summary
Allogeneic hematopoietic stem cell transplantation is increasingly used in the treatment of several diseases, especially hematological malignancies and disorders characterized by severe bone marrow failure [1,2,3,4]. The early studies showed that general T cell depletion was associated with a reduced risk of severe GVHD but an increased risk of leukemia relapse and graft failure [5], whereas more recent studies based on depletion of immunocompetent cell subsets are more promising [6,7,8,9,10]. The differentiation status of monocytes is altered with reduced production of pro-inflammatory cytokines and increased release of immunosuppressive IL-10. These effects seem to favor an immunosuppressive effect of G-CSF administration to healthy stem cell donors, but it should be emphasized that the question of donor heterogeneity has not been investigated in detail previously. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity
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