In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor

Haematologica. 2004 Dec;89(12):1517-24.


Background and objectives: Granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) transplantation is associated with a low incidence of graft-versus-host disease (GVHD) and has been used successfully in patients with human leukocyte antigen (HLA) matched/mismatched donors. This study evaluated the function of T cells and the quantities of immunological cells of G-BM.

Design and methods: Bone marrow was obtained from fifteen donors by aspiration. Lymphocyte proliferation ability, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) secreted by T cells were determined using a monotetrazolium (MTT) assay and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. T-cell subgroups, dendritic cell (DC) subsets, CD4(+)CD25(+) regulatory T cells and the expression of CD28/CD80/CD86 molecules on monocytes, B and T cells were analyzed using flow cytometry.

Results: G-CSF treatment decreased the quantities of IFN-gamma secretion dramatically (p=0.007) and IL-4 moderately (p=0.027), leading to higher ratios of IL-4/IFN-gamma (p=0.004). We confirmed T-cell hyporesponsiveness and lower expression of CD28/CD80/CD86 on monocytes, B and T cells. The absolute values of lymphocytes, T cell subgroups, CD3+CD4-CD8- cells, CD8+CD28- cells and B cells in bone marrow grafts were similar before and after G-CSF treatment. The number of monocytes per microliter was increased 2.13-fold, while the numbers of CD4(+)CD25(+) regulatory T cells were unchanged. DC2 were preferentially increased.

Interpretation and conclusions: Our results suggest that bone marrow T-cell hyporesponsiveness could be induced and that the increase of monocytes and DC2 and the downregulation of CD28/CD80/CD86 co-stimulatory signals were produced by in vivo use of G-CSF; this may be related to the preferential increase of monocytes and DC2 and the downregulation of CD28/CD80/CD86 co-stimulatory signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / analysis
  • B7-1 Antigen / analysis
  • B7-2 Antigen / analysis
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / immunology*
  • CD28 Antigens / analysis
  • Cell Count
  • Dendritic Cells / classification
  • Dendritic Cells / drug effects
  • Female
  • Filgrastim
  • Graft vs Host Disease / prevention & control
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Peripheral Blood Stem Cell Transplantation
  • Recombinant Proteins
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / immunology*


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Interleukin-4
  • Interferon-gamma
  • Filgrastim