Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets
BackgroundAllogeneic 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.Study d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00845/full |
| _version_ | 1818535969347862528 |
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| author | Guro Kristin Melve Guro Kristin Melve Elisabeth Ersvaer Geir Egil Eide Geir Egil Eide Einar K. Kristoffersen Einar K. Kristoffersen Øystein Bruserud Øystein Bruserud |
| author_facet | Guro Kristin Melve Guro Kristin Melve Elisabeth Ersvaer Geir Egil Eide Geir Egil Eide Einar K. Kristoffersen Einar K. Kristoffersen Øystein Bruserud Øystein Bruserud |
| author_sort | Guro Kristin Melve |
| collection | DOAJ |
| description | BackgroundAllogeneic 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.Study design and methodsWe 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.ResultsThe 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.ConclusionHealthy donors differ in their G-CSF responsiveness and preferential mobilization of immunocompetent cells. This difference seems to influence post-transplant recipient outcomes. |
| first_indexed | 2024-12-11T18:31:56Z |
| format | Article |
| id | doaj.art-bebd9f078ff04217afa7830e6d873c3e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T18:31:56Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bebd9f078ff04217afa7830e6d873c3e2022-12-22T00:54:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-05-01910.3389/fimmu.2018.00845330459Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte SubsetsGuro Kristin Melve0Guro Kristin Melve1Elisabeth Ersvaer2Geir Egil Eide3Geir Egil Eide4Einar K. Kristoffersen5Einar K. Kristoffersen6Øystein Bruserud7Øystein Bruserud8Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Biomedical Laboratory Sciences, Western Norway University of Applied Sciences, Bergen, NorwayCentre for Clinical Research, Haukeland University Hospital, Bergen, NorwayDepartment of Global Public Health and Primary Care, University of Bergen, Bergen, NorwayDepartment of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDivision for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, NorwayBackgroundAllogeneic 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.Study design and methodsWe 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.ResultsThe 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.ConclusionHealthy donors differ in their G-CSF responsiveness and preferential mobilization of immunocompetent cells. This difference seems to influence post-transplant recipient outcomes.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00845/fullapheresisgraft versus host diseasegranulocyte colony-stimulating factorhematopoietic stem cell mobilizationhematopoietic stem cell transplantationimmune reconstitution |
| spellingShingle | Guro Kristin Melve Guro Kristin Melve Elisabeth Ersvaer Geir Egil Eide Geir Egil Eide Einar K. Kristoffersen Einar K. Kristoffersen Øystein Bruserud Øystein Bruserud Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets Frontiers in Immunology apheresis graft versus host disease granulocyte colony-stimulating factor hematopoietic stem cell mobilization hematopoietic stem cell transplantation immune reconstitution |
| title | Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets |
| title_full | Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets |
| title_fullStr | Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets |
| title_full_unstemmed | Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets |
| title_short | Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets |
| title_sort | peripheral blood stem cell mobilization in healthy donors by granulocyte colony stimulating factor causes preferential mobilization of lymphocyte subsets |
| topic | apheresis graft versus host disease granulocyte colony-stimulating factor hematopoietic stem cell mobilization hematopoietic stem cell transplantation immune reconstitution |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00845/full |
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