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

Authors: Liang, HL  Yi, DH  Zheng, QJ  Du, JF  Cao, YX  Yu, SQ  Zhu, HL 
Citation: Liang HL, etal., Transplant Proc. 2008 Jun;40(5):1604-11. doi: 10.1016/j.transproceed.2008.02.078.
Pubmed: (View Article at PubMed) PMID:18589159
DOI: Full-text: DOI:10.1016/j.transproceed.2008.02.078

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.

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RGD Object Information
RGD ID: 11039422
Created: 2016-03-02
Species: All species
Last Modified: 2016-03-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.