FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/593723
Title:
FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells.
Authors:
Schildknecht, Anita; Brauer, Sabine; Brenner, Corinne; Lahl, Katharina; Schild, Hansjörg; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Probst, Hans Christian; van den Broek, Maries
Abstract:
Peripheral T-cell tolerance is thought to significantly contribute to the prevention of autoimmunity, and it has been shown that antigen-presenting steady-state dendritic cells efficiently induce peripheral tolerance. We previously showed that dendritic-cell-induced tolerance is a T-cell-intrinsic process that depends on coinhibitory molecules such as programmed death-1. Here we specifically analyze the involvement of FoxP3(+) regulatory T cells, which are known to be important for maintenance of self-tolerance. We show that antigen presentation by steady-state dendritic cells failed to induce peripheral tolerance in the absence of FoxP3(+) regulatory T cells but induced protective CD8(+) T-cell-mediated immunity instead. Regulatory T-cell-depleted mice had massively increased numbers of dendritic cells in lymph nodes. Dendritic cells isolated from mice without regulatory T cells had up-regulated costimulatory molecules and showed stronger T-cell stimulatory capacity ex vivo, suggesting that regulatory T cells contribute to peripheral tolerance by keeping the dendritic cells in an immature state. Using blocking antibodies, we demonstrate that CTLA-4 but not IL-10 is necessary for control of dendritic cells by regulatory T cells.
Affiliation:
TWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.
Citation:
FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. 2010, 107 (1):199-203 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
5-Jan-2010
URI:
http://hdl.handle.net/10033/593723
DOI:
10.1073/pnas.0910620107
PubMed ID:
20018763
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorSchildknecht, Anitaen
dc.contributor.authorBrauer, Sabineen
dc.contributor.authorBrenner, Corinneen
dc.contributor.authorLahl, Katharinaen
dc.contributor.authorSchild, Hansjörgen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorProbst, Hans Christianen
dc.contributor.authorvan den Broek, Mariesen
dc.date.accessioned2016-01-18T14:22:56Zen
dc.date.available2016-01-18T14:22:56Zen
dc.date.issued2010-01-05en
dc.identifier.citationFoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. 2010, 107 (1):199-203 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490en
dc.identifier.pmid20018763en
dc.identifier.doi10.1073/pnas.0910620107en
dc.identifier.urihttp://hdl.handle.net/10033/593723en
dc.description.abstractPeripheral T-cell tolerance is thought to significantly contribute to the prevention of autoimmunity, and it has been shown that antigen-presenting steady-state dendritic cells efficiently induce peripheral tolerance. We previously showed that dendritic-cell-induced tolerance is a T-cell-intrinsic process that depends on coinhibitory molecules such as programmed death-1. Here we specifically analyze the involvement of FoxP3(+) regulatory T cells, which are known to be important for maintenance of self-tolerance. We show that antigen presentation by steady-state dendritic cells failed to induce peripheral tolerance in the absence of FoxP3(+) regulatory T cells but induced protective CD8(+) T-cell-mediated immunity instead. Regulatory T-cell-depleted mice had massively increased numbers of dendritic cells in lymph nodes. Dendritic cells isolated from mice without regulatory T cells had up-regulated costimulatory molecules and showed stronger T-cell stimulatory capacity ex vivo, suggesting that regulatory T cells contribute to peripheral tolerance by keeping the dendritic cells in an immature state. Using blocking antibodies, we demonstrate that CTLA-4 but not IL-10 is necessary for control of dendritic cells by regulatory T cells.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntigens, CDen
dc.subject.meshCD8-Positive T-Lymphocytesen
dc.subject.meshCTLA-4 Antigenen
dc.subject.meshDendritic Cellsen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshImmune Toleranceen
dc.subject.meshInterleukin-10en
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Transgenicen
dc.subject.meshPhenotypeen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleFoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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