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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.
Xie, Yanhui; Wu, Min; Song, Runhua; Ma, Jiexian; Shi, Yi; Qin, Wenming; Jin, Youxin.
Afiliación
  • Xie Y; Department of Hematology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China. xyh@medmail.com.cn
Acta Biochim Biophys Sin (Shanghai) ; 41(9): 781-91, 2009 Sep.
Article en En | MEDLINE | ID: mdl-19727527
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.
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Bases de datos: MEDLINE Asunto principal: Dexametasona / Interleucina-2 / Linfocitos T Reguladores / Transfusión de Linfocitos / Enfermedad Injerto contra Huésped / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Acta Biochim Biophys Sin (Shanghai) Asunto de la revista: BIOFISICA / BIOQUIMICA Año: 2009 Tipo del documento: Article País de afiliación: China
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Bases de datos: MEDLINE Asunto principal: Dexametasona / Interleucina-2 / Linfocitos T Reguladores / Transfusión de Linfocitos / Enfermedad Injerto contra Huésped / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Acta Biochim Biophys Sin (Shanghai) Asunto de la revista: BIOFISICA / BIOQUIMICA Año: 2009 Tipo del documento: Article País de afiliación: China