Schildknecht, A; Brauer, S; Brenner, C; Lahl, K; Schild, H; Sparwasser, T; Probst, H C; van den Broek, M (2010). FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 107(1):199-203.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology|
|DDC:||610 Medicine & health|
|Date:||5 January 2010|
|Deposited On:||24 Mar 2010 16:21|
|Last Modified:||27 Nov 2013 19:53|
|Publisher:||National Academy of Sciences|
|Additional Information:||Copyright: National Academy of Sciences USA|
|Free access at:||Publisher DOI. An embargo period may apply.|
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