Improvement of heart allograft acceptability associated with recruitment of CD4+CD25+ T cells in peripheral blood by recipient treatment with granulocyte colony-stimulating factor

Transplant Proc. 2008 Jun;40(5):1604-11. doi: 10.1016/j.transproceed.2008.02.078.

Abstract

Background: Granulocyte colony-stimulating factor (G-CSF), an important hematopoietic growth factor of the myeloid lineage, exerts profound immunoregulatory effects in T-cell tolerance. The study objective was to investigate the potential mechanism of G-CSF's antirejection effects in a fully mismatched rat cardiac allograft model.

Methods: The allograft recipients were treated with subcutaneous injection of recombinant human G-CSF (rh-G-CSF) at a dose of 250 microg/kg/d for 6 days starting from the day of cardiac transplantation. The alloreactive T-cell response and rejection level of G-CSF-treated rats were compared with those of control rats using mixed lymphocyte reactions (MLR) and histological examinations. Cytokine and cellular profiles were determined using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The presence and suppressive functions of regulatory T cells were determined by adoptive cell transfer experiments.

Results: Posttransplantation treatment of recipients with rh-G-CSF alone prolonged allograft survival, improved allograft biopsy grading scores, and induced alloreactive T-cell hyporesponsiveness accompanied by high levels of interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) production in MLR. It also enhanced CD4+CD25+ T cells in peripheral blood. The splenocytes from rh-G-CSF-treated recipients transferred antirejection effects to secondary recipients.

Conclusions: Posttransplantation treatment of cardiac allograft recipients with rh-G-CSF leads to alloreactive T-cell hyporesponsiveness in vivo and in vitro associated with recruitment of CD4+CD25+ T cells in the peripheral blood. This study may provide insight into the application of G-CSF to control acute rejection of solid organ transplantations.

MeSH terms

  • Abdomen
  • Animals
  • Antigens, CD / immunology
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Heart Transplantation / immunology*
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Male
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / immunology*
  • Transplantation, Heterotopic
  • Transplantation, Homologous / immunology

Substances

  • Antigens, CD
  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor