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

J Transl Med. 2015 May 7;13:145. doi: 10.1186/s12967-015-0507-z.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Transplantation*
  • CD4-Positive T-Lymphocytes / cytology
  • Female
  • Flow Cytometry
  • Graft vs Host Disease / prevention & control
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Ionomycin / chemistry
  • Ki-67 Antigen / metabolism
  • Lectins, C-Type / metabolism
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation*
  • T-Lymphocytes, Regulatory / cytology*
  • Tetradecanoylphorbol Acetate
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • IFNG protein, human
  • IL17A protein, human
  • IL2RA protein, human
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Ki-67 Antigen
  • Lectins, C-Type
  • Granulocyte Colony-Stimulating Factor
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate