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dc.contributor.authorBjarnadottir, Una
dc.contributor.authorLemarquis, Andri L
dc.contributor.authorHalldorsdottir, Snaefridur
dc.contributor.authorFreysdottir, Jona
dc.contributor.authorLudviksson, Bjorn R
dc.date.accessioned2014-10-09T14:43:39Z
dc.date.available2014-10-09T14:43:39Z
dc.date.issued2014-07-19
dc.date.submitted2014
dc.identifier.citationScand. J. Immunol. 2014;80(5):313-22en
dc.identifier.issn1365-3083
dc.identifier.pmid25039313
dc.identifier.doi10.1111/sji.12212
dc.identifier.urihttp://hdl.handle.net/2336/332606
dc.description.abstractCD8+ Tregs display an immunoregulatory activity and may play an essential role in the immunopathology of several diseases. Therefore, their therapeutic potential is exquisite and further studies on their differentiation and function is essential. The aim of this study was to evaluate the role of the innate immune system in CD8+ iTreg differentiation and function. Naive human CD8+CD25-CD45RA+ T-cells were cultured in Treg-inducing conditions with or without IL-1β, TNFα or monocyte-derived dendritic cells (DCs). The differentiation of CD8+CD127-CD25(hi) FoxP3(hi) induced Tregs (CD8+ iTregs) is dependent on TGF-β1 and IL-2, which had synergistic effect upon their differentiation. CD8+ iTregs were also induced in a co-culture with allogeneic mature DCs (mDCs). The CD8+ iTregs suppressive function was confirmed, which was diminished in the presence of IL-1β and TNFα. The IL-1β prevented suppressive function was associated with reduced secretion of IL-10 and IFNγ whereas the presence of TNFα did not affect their secretion. Furthermore, the presence of TNFα reduced IL-10 and TGF-β1 secretion by CD8+ iTregs whereas only IL-10 secretion was decreased by IL-1β. Together, these results suggest that IL-1β and TNFα prevent IL-2 and TGF-β1 driven CD8+ iTregs suppressive function in human T-cells. Such pro-inflammatory innate immune response possibly mediates its negative tolerogenic effect through reduced IFNγ, IL-10 and TGF-β1 driven mechanism. This article is protected by copyright. All rights reserved.
dc.languageENG
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1111/sji.12212en
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/sji.12212/pdfen
dc.rightsArchived with thanks to Scandinavian journal of immunologyen
dc.subject.meshTransforming Growth Factor beta1en
dc.subject.meshAntigens, CD28/biosynthesisen
dc.subject.meshCD8-Positive T-Lymphocytes/drug effectsen
dc.subject.meshCD8-Positive T-Lymphocytes/immunology*en
dc.subject.meshCell Differentiation/immunologyen
dc.subject.meshCells, Cultureden
dc.subject.meshCoculture Techniquesen
dc.subject.meshDendritic Cells/immunologyen
dc.subject.meshHumansen
dc.subject.meshImmune Tolerance*en
dc.subject.meshImmunity, Innate*en
dc.subject.meshInterferon-gamma/immunologyen
dc.subject.meshInterleukin-10/immunologyen
dc.subject.meshInterleukin-1beta/immunology*en
dc.subject.meshInterleukin-1beta/pharmacologyen
dc.subject.meshInterleukin-2/immunologyen
dc.subject.meshInterleukin-2/pharmacologyen
dc.subject.meshLymphocyte Activation/immunologyen
dc.subject.meshT-Lymphocytes, Regulatory/drug effectsen
dc.subject.meshT-Lymphocytes, Regulatory/immunology*en
dc.subject.meshTransforming Growth Factor beta1/immunologyen
dc.subject.meshTumor Necrosis Factor-alpha/immunology*en
dc.subject.meshTumor Necrosis Factor-alpha/pharmacologyen
dc.titleThe suppressive function of human CD8+ iTregs is inhibited by IL-1β and TNFαen
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Landspitali - The National University Hospital of Iceland.en
dc.identifier.journalScandinavian journal of immunologyen
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractCD8+ Tregs display an immunoregulatory activity and may play an essential role in the immunopathology of several diseases. Therefore, their therapeutic potential is exquisite and further studies on their differentiation and function is essential. The aim of this study was to evaluate the role of the innate immune system in CD8+ iTreg differentiation and function. Naive human CD8+CD25-CD45RA+ T-cells were cultured in Treg-inducing conditions with or without IL-1β, TNFα or monocyte-derived dendritic cells (DCs). The differentiation of CD8+CD127-CD25(hi) FoxP3(hi) induced Tregs (CD8+ iTregs) is dependent on TGF-β1 and IL-2, which had synergistic effect upon their differentiation. CD8+ iTregs were also induced in a co-culture with allogeneic mature DCs (mDCs). The CD8+ iTregs suppressive function was confirmed, which was diminished in the presence of IL-1β and TNFα. The IL-1β prevented suppressive function was associated with reduced secretion of IL-10 and IFNγ whereas the presence of TNFα did not affect their secretion. Furthermore, the presence of TNFα reduced IL-10 and TGF-β1 secretion by CD8+ iTregs whereas only IL-10 secretion was decreased by IL-1β. Together, these results suggest that IL-1β and TNFα prevent IL-2 and TGF-β1 driven CD8+ iTregs suppressive function in human T-cells. Such pro-inflammatory innate immune response possibly mediates its negative tolerogenic effect through reduced IFNγ, IL-10 and TGF-β1 driven mechanism. This article is protected by copyright. All rights reserved.


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