title: Improvement of heart allograft acceptability associated with recruitment of CD4+CD25+ T cells in peripheral blood by recipient treatment with granulocyte colony-stimulating factor.
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.
authors.affiliation: Department of Cardiovascular Surgery, Institute of Cardiovascular Disease, Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: H L
authors.initials: HL
authors.lastname: Liang
authors.forename: D H
authors.initials: DH
authors.lastname: Yi
authors.forename: Q J
authors.initials: QJ
authors.lastname: Zheng
authors.forename: J F
authors.initials: JF
authors.lastname: Du
authors.forename: Y X
authors.initials: YX
authors.lastname: Cao
authors.forename: S Q
authors.initials: SQ
authors.lastname: Yu
authors.forename: H L
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000005:Abdomen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor