FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells
| Autor: | Corinne Brenner, Hans Christian Probst, Sabine Brauer, Katharina Lahl, Tim Sparwasser, Anita Schildknecht, Hansjörg Schild, Maries van den Broek |
|---|---|
| Přispěvatelé: | TWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany., University of Zurich |
| Rok vydání: | 2009 |
| Předmět: |
Antigen presentation
610 Medicine & health Mice Transgenic Biology CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Immune tolerance Mice Antigens CD Immune Tolerance Animals CTLA-4 Antigen IL-2 receptor Antigen-presenting cell 1000 Multidisciplinary Multidisciplinary Follicular dendritic cells Peripheral tolerance FOXP3 Forkhead Transcription Factors Dendritic Cells Biological Sciences Natural killer T cell Cell biology Interleukin-10 Mice Inbred C57BL Phenotype 10032 Clinic for Oncology and Hematology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 107(1) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|