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Glucocorticoid amplifies IL-2-dependent expansion offunctional FoxP3+CD4+CD25+T regulatory cellsin vivoand enhances their capacity to suppress EAE
Xin Chen1; Joost J. Oppenheim2; Robin T. Winkler-Pickett3; John R. Ortaldo3; O. M. Zack Howard2
2006-08
Source PublicationEUROPEAN JOURNAL OF IMMUNOLOGY
ISSN0014-2980
Volume36Issue:8Pages:2139-2149
Abstract

IL-2 is crucial for the production of CD4+CD25+T regulatory (Treg) cells whileimportant for the generation of effective T cell-mediated immunity. How to exploit thecapacity of IL-2 to expand Treg cells, while restraining activation of T effector (Teff)cells, is an important and unanswered therapeutic question. Dexamethasone (Dex), asynthetic glucocorticoid steroid, has been reported to suppress IL-2-mediated activationof Teff cells and increase the proportion of Treg cells. Thus, we hypothesized thatglucocorticoids may be useful as costimulants to amplify IL-2-mediated selectiveexpansion of Treg cells. We show in this study that short-term simultaneousadministration of Dex and IL-2 markedly expanded functional suppressiveFoxp3+CD4+CD25+T cells in murine peripheral lymphoid tissues. In a myelinoligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis(EAE) mouse model, we observed that splenic CD4+CD25+Tcells failed to suppress theproliferation of CD4+CD25–T cells. Pretreatment with Dex/IL-2 remarkably increasedthe proportion of CD4+FoxP3+cells and partially restored the function of splenicCD4+CD25+Tcells, and inhibited the development of EAE. Therefore, the combinationof glucocorticoid and IL-2, two currently used therapeutics, may provide a novelapproach for the treatment of autoimmune diseases, transplant rejection and graft-vs.-host disease.

Keywordcd4+cd25+t Regulatory Cells Dexamethasone Experimental Autoimmune Encephalomyelitis Il-2
DOI10.1002/eji.200635873
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000239855900014
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Cited Times [WOS]:151   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXin Chen
Affiliation1.Basic Research Program, SAIC-Frederick, Center for Cancer Research, NationalCancer Institute-Frederick, National Institutes of Health, Frederick, MD, USA
2.Laboratory of Molecular Immunoregulation, Center for Cancer Research, NationalCancer Institute-Frederick, National Institutes of Health, Frederick, MD, USA
3.Laboratory of Experimental Immunology, Center for Cancer Research, NationalCancer Institute-Frederick, National Institutes of Health, Frederick, MD, USA
Recommended Citation
GB/T 7714
Xin Chen,Joost J. Oppenheim,Robin T. Winkler-Pickett,et al. Glucocorticoid amplifies IL-2-dependent expansion offunctional FoxP3+CD4+CD25+T regulatory cellsin vivoand enhances their capacity to suppress EAE[J]. EUROPEAN JOURNAL OF IMMUNOLOGY,2006,36(8):2139-2149.
APA Xin Chen,Joost J. Oppenheim,Robin T. Winkler-Pickett,John R. Ortaldo,&O. M. Zack Howard.(2006).Glucocorticoid amplifies IL-2-dependent expansion offunctional FoxP3+CD4+CD25+T regulatory cellsin vivoand enhances their capacity to suppress EAE.EUROPEAN JOURNAL OF IMMUNOLOGY,36(8),2139-2149.
MLA Xin Chen,et al."Glucocorticoid amplifies IL-2-dependent expansion offunctional FoxP3+CD4+CD25+T regulatory cellsin vivoand enhances their capacity to suppress EAE".EUROPEAN JOURNAL OF IMMUNOLOGY 36.8(2006):2139-2149.
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