Regulatory T Cell Suppression and Anergy Are Differentially Regulated by Proinflammatory Cytokines Produced by TLR-Activated Dendritic Cells

CD25(+)CD4(+) regulatory T cells (Tregs) are required for the maintenance of peripheral tolerance to certain self Ags. In this study, the requirements for murine Treg-suppressive activity and proliferation were examined in the context of the maturation of myeloid dendritic cells (DCs). We find that...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-12, Vol.173 (12), p.7249-7258
Main Authors: Kubo, Takekazu, Hatton, Robin D, Oliver, James, Liu, Xiaofen, Elson, Charles O, Weaver, Casey T
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - physiology
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - immunology
Bone Marrow Cells - metabolism
Cell Proliferation
Cells, Cultured
Clonal Anergy - immunology
Cytokines - biosynthesis
Cytokines - physiology
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Drug Synergism
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Inflammation Mediators - metabolism
Inflammation Mediators - physiology
Interleukin-1 - physiology
Interleukin-2 - pharmacology
Interleukin-6 - physiology
Lipopolysaccharides - pharmacology
Membrane Glycoproteins - physiology
Mice
Mice, Congenic
Mice, Inbred BALB C
Mice, Inbred C3H
Receptors, Cell Surface - physiology
Receptors, Interleukin-2 - biosynthesis
Signal Transduction - immunology
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Toll-Like Receptors
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Summary:CD25(+)CD4(+) regulatory T cells (Tregs) are required for the maintenance of peripheral tolerance to certain self Ags. In this study, the requirements for murine Treg-suppressive activity and proliferation were examined in the context of the maturation of myeloid dendritic cells (DCs). We find that the suppressive function of Tregs is critically dependent on immature DCs and is readily reversed by the maturation of DCs induced by GM-CSF, but does not require TLR activation of either DCs or Tregs. In contrast, reversal of Treg anergy is dependent on TLR activation of DCs, and involves the potentiation of Treg responsiveness to IL-2 by cooperative effects of IL-6 and IL-1, both of which are produced by TLR-activated, mature DCs. Thus, proinflammatory cytokines produced by TLR-activated, mature DCs are required for reversal of Treg anergy, but are not required to overcome Treg suppression.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.12.7249