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Article: Regulation of rat and human T-cell immune response by pharmacologically modified dendritic cells

TitleRegulation of rat and human T-cell immune response by pharmacologically modified dendritic cells
Authors
Issue Date2009
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com
Citation
Transplantation, 2009, v. 87 n. 11, p. 1617-1628 How to Cite?
AbstractBACKGROUND: The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4+CD25+ T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems. METHODS: After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4+CD25+ regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA. RESULTS: In this study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4+CD25+ regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL)-2 by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10. CONCLUSION: These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.
Persistent Identifierhttp://hdl.handle.net/10722/197251
ISSN
2015 Impact Factor: 3.69
2015 SCImago Journal Rankings: 1.699
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFazekasova, Hen_US
dc.contributor.authorGolshayan, Den_US
dc.contributor.authorRead, Jen_US
dc.contributor.authorTsallios, Aen_US
dc.contributor.authorTsang, JYSen_US
dc.contributor.authorDorling, Aen_US
dc.contributor.authorGeorge, Aen_US
dc.contributor.authorLechler, Ren_US
dc.contributor.authorLombardi, Gen_US
dc.contributor.authorMirenda, Ven_US
dc.date.accessioned2014-05-23T02:30:03Z-
dc.date.available2014-05-23T02:30:03Z-
dc.date.issued2009en_US
dc.identifier.citationTransplantation, 2009, v. 87 n. 11, p. 1617-1628en_US
dc.identifier.issn0041-1337-
dc.identifier.urihttp://hdl.handle.net/10722/197251-
dc.description.abstractBACKGROUND: The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4+CD25+ T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems. METHODS: After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4+CD25+ regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA. RESULTS: In this study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4+CD25+ regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL)-2 by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10. CONCLUSION: These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com-
dc.relation.ispartofTransplantationen_US
dc.subject.meshDendritic Cells - drug effects - immunology-
dc.subject.meshDexamethasone - pharmacology-
dc.subject.meshImmune System Processes - immunology-
dc.subject.meshImmune Tolerance - drug effects - immunology-
dc.subject.meshT-Lymphocytes - immunology-
dc.titleRegulation of rat and human T-cell immune response by pharmacologically modified dendritic cellsen_US
dc.typeArticleen_US
dc.identifier.emailTsang, JYS: jystsang@hkucc.hku.hken_US
dc.identifier.doi10.1097/TP.0b013e3181a5504c-
dc.identifier.pmid19502952-
dc.identifier.hkuros160626en_US
dc.identifier.volume87en_US
dc.identifier.issue11en_US
dc.identifier.spage1617en_US
dc.identifier.epage1628en_US
dc.identifier.isiWOS:000266889900004-
dc.publisher.placeUnited States-

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