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dc.contributor.authorGunnlaugsdottir, B
dc.contributor.authorMaggadottir, S M
dc.contributor.authorSkaftadottir, I
dc.contributor.authorLudviksson, B R
dc.date.accessioned2014-02-24T15:34:03Z
dc.date.available2014-02-24T15:34:03Z
dc.date.issued2013-02
dc.date.submitted2013
dc.identifier.citationScand. J. Immunol. 2013, 77 (2):125-34en
dc.identifier.issn1365-3083
dc.identifier.pmid23126599
dc.identifier.doi10.1111/sji.12009
dc.identifier.urihttp://hdl.handle.net/2336/313315
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en
dc.description.abstractThe expression of the integrin αE (CD103), may enhance the retention of regulatory T cells to peripheral inflammatory sites and possibly contribute to their suppressive potential. The aim of this study was to define the regulatory role of IL-2 and TGF-β1 on the CD103 expression and the optimal in vitro conditions for the induction/expansion of human CD4(+) and CD8(+) Tregs. Cord blood mononuclear cells (CBMC) were stimulated under various culture conditions, including anti-CD3, anti-CD28, IL-2 and TGF-β1. TGF-β1 and IL-2 were both required for optimal expression of CD103. In addition, TGF-β1 and IL-2 synergistically induced CD103 expression on CD8(+) T cells, whereas, only additive induced expression was noted on CD4(+) T cells. Surprisingly, CD103 expression was not dependent upon CD28 costimulation. IL-2 also played a central role in CD103 expression by CD25(hi) Foxp3+ Tregs. IL-2, TGF-β1 and anti-CD3 defined the optimal stimulatory conditions favouring the induction/expansion of both CD4(+) and CD8(+) human Tregs from naive CBMC. Thus, this study provides new insights into the regulatory role of IL-2 upon CD103 expression by human cord blood CD4(+) and CD8(+) T cells. Furthermore, it identifies the in vitro culture conditions driving the differentiation of the novel phenotype CD4(+) and CD8(+) CD103(+) CD25(hi) Foxp3+ Tregs from human CBMC.
dc.description.sponsorshipLandspitali University Hospital Research Fund, University of Iceland Research Funden
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.relation.urlhttp://dx.doi.org/10.1111/sji.12009en
dc.rightsArchived with thanks to Scandinavian journal of immunologyen
dc.subjectFrumurannsókniren
dc.subject.meshAntigens, CDen
dc.subject.meshAntigens, CD4en
dc.subject.meshAntigens, CD8en
dc.subject.meshCells, Cultureden
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHumansen
dc.subject.meshImmunophenotypingen
dc.subject.meshIntegrin alpha Chainsen
dc.subject.meshInterleukin-2en
dc.subject.meshInterleukin-2 Receptor alpha Subuniten
dc.subject.meshPhenotypeen
dc.subject.meshProtein-Serine-Threonine Kinasesen
dc.subject.meshReceptors, Transforming Growth Factor betaen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshTransforming Growth Factor beta1en
dc.titleThe ex vivo induction of human CD103⁺ CD25hi Foxp3⁺ CD4⁺ and CD8⁺ Tregs is IL-2 and TGF-β1 dependent.en
dc.typeArticleen
dc.contributor.departmentUniv Hosp, Landspitali, Dept Immunol, IS-101 Reykjavik, Iceland, Univ Iceland, Fac Med, Reykjavik, Icelanden
dc.identifier.journalScandinavian journal of immunologyen
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractThe expression of the integrin αE (CD103), may enhance the retention of regulatory T cells to peripheral inflammatory sites and possibly contribute to their suppressive potential. The aim of this study was to define the regulatory role of IL-2 and TGF-β1 on the CD103 expression and the optimal in vitro conditions for the induction/expansion of human CD4(+) and CD8(+) Tregs. Cord blood mononuclear cells (CBMC) were stimulated under various culture conditions, including anti-CD3, anti-CD28, IL-2 and TGF-β1. TGF-β1 and IL-2 were both required for optimal expression of CD103. In addition, TGF-β1 and IL-2 synergistically induced CD103 expression on CD8(+) T cells, whereas, only additive induced expression was noted on CD4(+) T cells. Surprisingly, CD103 expression was not dependent upon CD28 costimulation. IL-2 also played a central role in CD103 expression by CD25(hi) Foxp3+ Tregs. IL-2, TGF-β1 and anti-CD3 defined the optimal stimulatory conditions favouring the induction/expansion of both CD4(+) and CD8(+) human Tregs from naive CBMC. Thus, this study provides new insights into the regulatory role of IL-2 upon CD103 expression by human cord blood CD4(+) and CD8(+) T cells. Furthermore, it identifies the in vitro culture conditions driving the differentiation of the novel phenotype CD4(+) and CD8(+) CD103(+) CD25(hi) Foxp3+ Tregs from human CBMC.


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