FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells.
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Authors
Schildknecht, AnitaBrauer, Sabine
Brenner, Corinne
Lahl, Katharina
Schild, Hansjörg
Sparwasser, Tim
Probst, Hans Christian
van den Broek, Maries
Issue Date
2010-01-05
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Show full item recordAbstract
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.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.Affiliation
TWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.PubMed ID
20018763Type
ArticleLanguage
enISSN
1091-6490ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0910620107
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