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Acta Biochimica et Biophysica Sinica Advance Access originally published online on July 25, 2009
Acta Biochimica et Biophysica Sinica 2009 41(9):781-791; doi:10.1093/abbs/gmp067
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

A glucocorticoid amplifies IL-2-induced selective expansion of CD4+CD25+FOXP3+ regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation

Yanhui Xie1,*, Min Wu1, Runhua Song1, Jiexian Ma1, Yi Shi2, Wenming Qin2 and Youxin Jin2,*

1 Department of Hematology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
2 Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China

* Correspondence address. Tel: +86-21-52889999; Fax: +86-2162489191; E-mail: xyh{at}medmail.com.cn (Y.X.); Tel: +86-21-54921222; Fax: +86-2154921011; E-mail: yxjin{at}sibs.ac.cn (Y.J.)


   Abstract

Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously administered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4+CD25+FOXP3+ T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/Teff) ratio to prevent graft-versus-host disease (GVHD). After combined treatment of the donor with Dex (5 mg/kg/day) and IL-2 (300,000 IU/mouse/day) for 3 days, grafts were subjected to flow cytometric analysis, and transplantation was carried out from male C57BL/6 mice to female BALB/c mice aged 8–12 weeks. Results showed that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive CD4+CD25+FOXP3+ T cells in the murine spleen. In this murine allogeneic transplantation model, the grafts from donors with Dex and IL-2 pre-treatment led to a longer survival time for the recipients than for the control group (median survival time > 60 day vs. 12 day, P = 0.0002). The ratio of Treg/Teff also increased remarkably (0.43 ± 0.15 vs. 0.14 ± 0.01, P = 0.01). This study demonstrated that co-stimulation with Dex and IL-2 selectively expanded functional CD4+CD25+FOXP3+ T cells in vivo, and that grafts from donors pre-treated with Dex and IL-2 led to longer survival time and greater suppression of GVHD after allogeneic transplantation. Thus, GVHD can be suppressed by the specific expansion of regulatory T cells with Dex and IL-2 in graft donors.

Keywords    glucocorticoid; dexamethasone; interleukin-2; regulatory T cell; graft-versus-host disease

Received: May 8, 2009; Accepted: June 1, 2009
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