Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect

Int J Hematol. 2004 Feb;79(2):178-84. doi: 10.1532/ijh97.a10227.


Whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects lymphocyte function directly or indirectly is controversial. In this study, we found that T-cell proliferation was decreased considerably in response to phytohemagglutinin in donors who received rhG-CSF but was partly restored after monocytes were removed. Intracellular cytokine staining revealed that the interferon gamma-interleukin 4 ratio decreased by 5.97-fold in donor CD4+ cells after rhG-CSF treatment. No effect of rhG-CSF on ex vivo T-cell function was observed. rhG-CSF indirectly induced significant quantitative and qualitative changes on lymphocytes, including a decrease in T-cell proliferation and type 2 helper T-cell polarization of the cytokine profile. Although monocytes suppressed T-cell proliferation, the suppressive activity induced by the quantitative change in monocyte numbers cannot completely account for the hyporesponsiveness of T-lymphocytes. We believe that there must be another mediating factor. In addition, the numbers and mean fluorescence intensities of CD14CD86+ cells and CD19+CD80+ cells declined significantly in the peripheral blood after rhG-CSF treatment. Suboptimal amounts of stimulatory signals provided by low expression levels of B7 molecules on antigen-presenting cells (monocytes, B-lymphocytes) may help explain the alteration in T-cell proliferation. In addition, the absolute counts of CD3+CD4-CD8 cells in the peripheral blood were markedly increased and enriched in leukapheresis products following G-CSF treatment. These suppressor cells may contribute to T-cell hyporesponsiveness.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / metabolism
  • B7-1 Antigen / metabolism
  • Cell Division / drug effects
  • Cell Division / immunology
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Leukapheresis
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism
  • Recombinant Proteins
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Antigens, CD19
  • B7-1 Antigen
  • Lipopolysaccharide Receptors
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Interleukin-4
  • Interferon-gamma