Recombinant human granulocyte colony-stimulating factor significantly decreases the expression of CXCR3 and CCR6 on T cells and preferentially induces T helper cells to a T helper 17 phenotype in peripheral blood harvests

Biol Blood Marrow Transplant. 2009 Jul;15(7):835-43. doi: 10.1016/j.bbmt.2009.03.016.

Abstract

The aim of this study was to investigate the expression of chemokine receptors on T cells and functional changes of T helper (Th) cells in peripheral blood stem cell (PBSC) harvests after treating healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Using multiparameter flow cytometry, we analyzed the expression of CXCR3 and CCR6 on T cells and the production of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-17 by CD4(+) Th cells in PBSC grafts of healthy donors after in vivo rhG-CSF application. Alterations in the relative expression levels of T cell receptor beta variable (TCRBV) family members were determined using real-time polymerase chain reaction (PCR). rhG-CSF mobilization significantly decreased the expression of CXCR3 and CCR6 on T cells. Treating donors with rhG-CSF resulted in decreased IFN-gamma production and dramatically increased IL-4 and IL-17 secretion by CD4(+) Th cells, leading to T cell polarization from the Th1 to the Th2 phenotype and a preferential increase in IL-17-producing CD4(+) Th cells. We did not observe any differences in the relative expression levels of TCRBV family members before and after in vivo rhG-CSF application. Our results suggest that the expression of CXCR3 and CCR6 on donor T cells was dramatically downregulated and an IL-17 phenotype of CD4(+) Th cells was preferentially induced in PBSC grafts after treating healthy donors with rhG-CSF. The observed effects of rhG-CSF on T cells may be independent of the relative expression levels of TCRBV family members.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Gene Expression Regulation / drug effects*
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Hematopoietic Stem Cells*
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Living Donors
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, CCR6 / biosynthesis*
  • Receptors, CXCR3 / biosynthesis*
  • Recombinant Proteins
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • CCR6 protein, human
  • CXCR3 protein, human
  • IL4 protein, human
  • Interleukin-17
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, CCR6
  • Receptors, CXCR3
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Interleukin-4