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Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts

BACKGROUND: Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G...

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Autores principales: Zhao, Xiang-Yu, Wang, Yu-Tong, Mo, Xiao-Dong, Zhao, Xiao-Su, Wang, Ya-Zhe, Chang, Ying-Jun, Huang, Xiao-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490623/
https://www.ncbi.nlm.nih.gov/pubmed/25948100
http://dx.doi.org/10.1186/s12967-015-0507-z
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author Zhao, Xiang-Yu
Wang, Yu-Tong
Mo, Xiao-Dong
Zhao, Xiao-Su
Wang, Ya-Zhe
Chang, Ying-Jun
Huang, Xiao-Jun
author_facet Zhao, Xiang-Yu
Wang, Yu-Tong
Mo, Xiao-Dong
Zhao, Xiao-Su
Wang, Ya-Zhe
Chang, Ying-Jun
Huang, Xiao-Jun
author_sort Zhao, Xiang-Yu
collection PubMed
description BACKGROUND: Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB). METHOD: G-BM and G-PB were obtained from 20 allogeneic donors. T-cell subgroups, including conventional T cells and different types of Treg cells, as well as the percentage of Ki67 expression on CD4(+)CD25(high)Foxp3(+) Treg cells, were analyzed using flow cytometry. The levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17) secreted by T cells stimulated with PMA and ionomycin were also determined by flow cytometry. RESULTS: The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg cells was significantly higher in the G-BM group, with higher proportions of CD45RA(+) naïve Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05). The percentage of Ki67 expression in CD4(+)CD25(high)Foxp3(+) Treg cells in G-BM was significantly higher than that on G-PB. The suppressive functions of Treg cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The proportions of CD4(+)CD25(−)CD69(+) Treg subsets as well as Th1 cells in G-BM were also significantly higher than those in G-PB (P < 0.001). The proportions of conventional T cells and Th17 effector cells were comparable in G-BM compared with those in G-PB. Thus, the ratio of conventional T cells and CD4(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G-PB (P = 0.014). CONCLUSION: In addition to the much higher T-cell counts in G-PB grafts that may contribute to more severe GVHD, the higher frequency of Treg cells and lower ratio of conventional T cells to Treg cells in G-BM compared with G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0507-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-44906232015-07-04 Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts Zhao, Xiang-Yu Wang, Yu-Tong Mo, Xiao-Dong Zhao, Xiao-Su Wang, Ya-Zhe Chang, Ying-Jun Huang, Xiao-Jun J Transl Med Research BACKGROUND: Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB). METHOD: G-BM and G-PB were obtained from 20 allogeneic donors. T-cell subgroups, including conventional T cells and different types of Treg cells, as well as the percentage of Ki67 expression on CD4(+)CD25(high)Foxp3(+) Treg cells, were analyzed using flow cytometry. The levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17) secreted by T cells stimulated with PMA and ionomycin were also determined by flow cytometry. RESULTS: The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg cells was significantly higher in the G-BM group, with higher proportions of CD45RA(+) naïve Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05). The percentage of Ki67 expression in CD4(+)CD25(high)Foxp3(+) Treg cells in G-BM was significantly higher than that on G-PB. The suppressive functions of Treg cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The proportions of CD4(+)CD25(−)CD69(+) Treg subsets as well as Th1 cells in G-BM were also significantly higher than those in G-PB (P < 0.001). The proportions of conventional T cells and Th17 effector cells were comparable in G-BM compared with those in G-PB. Thus, the ratio of conventional T cells and CD4(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G-PB (P = 0.014). CONCLUSION: In addition to the much higher T-cell counts in G-PB grafts that may contribute to more severe GVHD, the higher frequency of Treg cells and lower ratio of conventional T cells to Treg cells in G-BM compared with G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0507-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-07 /pmc/articles/PMC4490623/ /pubmed/25948100 http://dx.doi.org/10.1186/s12967-015-0507-z Text en © Zhao et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhao, Xiang-Yu
Wang, Yu-Tong
Mo, Xiao-Dong
Zhao, Xiao-Su
Wang, Ya-Zhe
Chang, Ying-Jun
Huang, Xiao-Jun
Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title_full Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title_fullStr Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title_full_unstemmed Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title_short Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts
title_sort higher frequency of regulatory t cells in granulocyte colony-stimulating factor (g-csf)-primed bone marrow grafts compared with g-csf-primed peripheral blood grafts
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490623/
https://www.ncbi.nlm.nih.gov/pubmed/25948100
http://dx.doi.org/10.1186/s12967-015-0507-z
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