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Toll Pathway-Dependent Blockade of CD4+CD25+ T Cell-Mediated Suppression by Dendritic Cells
Chandrashekhar Pasare,Ruslan Medzhitov*
Toll-like receptors (TLRs) control activation of adaptive immune
responses by antigen-presenting cells (APCs). However, initiationof
adaptive immune responses is also controlled by regulatoryT cells
(TR cells), which act to prevent activation of
autoreactiveT cells. Here we describe a second mechanism of immune
inductionby TLRs, which is independent of effects on costimulation.
Microbialinduction of the Toll pathway blocked the suppressive effect
ofCD4+CD25+ TR cells, allowing
activation of pathogen-specific adaptive immuneresponses. This block
of suppressor activity was dependent inpart on interleukin-6, which
was induced by TLRs upon recognitionof microbial products.
Howard Hughes Medical Institute and Section of Immunobiology, Yale
University School of Medicine, New Haven, CT 06520, USA.
*
To whom correspondence should be addressed. E-mail:
ruslan.medzhitov{at}yale.edu
The editors suggest the following Related Resources on Science sites:
Fiona Powrie and Kevin J. Maloy (14 February 2003) Science299 (5609), 1030.
[DOI: 10.1126/science.1082031] |Summary »|Full Text »|PDF »
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G. W. Jones, R. M. McLoughlin, V. J. Hammond, C. R. Parker, J. D. Williams, R. Malhotra, J. Scheller, A. S. Williams, S. Rose-John, N. Topley, et al. (2010)
J. Immunol.
184, 2130-2139
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Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition.
Immunostimulatory RNA Blocks Suppression by Regulatory T Cells.
D. Anz, V. H. Koelzer, S. Moder, R. Thaler, T. Schwerd, K. Lahl, T. Sparwasser, R. Besch, H. Poeck, V. Hornung, et al. (2010)
J. Immunol.
184, 939-946
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Mammalian Target of Rapamycin Inhibition and Alloantigen-Specific Regulatory T Cells Synergize To Promote Long-Term Graft Survival in Immunocompetent Recipients.
G. Raimondi, T. L. Sumpter, B. M. Matta, M. Pillai, N. Corbitt, Y. Vodovotz, Z. Wang, and A. W. Thomson (2010)
J. Immunol.
184, 624-636
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A Dual Action of Rheumatoid Arthritis Synovial Fibroblast IL-15 Expression on the Equilibrium between CD4+CD25+ Regulatory T Cells and CD4+CD25- Responder T Cells.
M. Benito-Miguel, Y. Garcia-Carmona, A. Balsa, C. Perez de Ayala, T. Cobo-Ibanez, E. Martin-Mola, and M.-E. Miranda-Carus (2009)
J. Immunol.
183, 8268-8279
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FOXP3-enriched infiltrates associated with better outcome in renal allografts with inflamed fibrosis.
J. Zuber, A. Brodin-Sartorius, N. Lapidus, N. Patey, M. Tosolini, S. Candon, M. Rabant, R. Snanoudj, C. Panterne, E. Thervet, et al. (2009)
Nephrol. Dial. Transplant.
24, 3847-3854
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Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus.
A. Lartigue, N. Colliou, S. Calbo, A. Francois, S. Jacquot, C. Arnoult, F. Tron, D. Gilbert, and P. Musette (2009)
J. Immunol.
183, 6207-6216
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Targeting a Mimotope Vaccine to Activating Fc{gamma} Receptors Empowers Dendritic Cells to Prime Specific CD8+ T Cell Responses in Tumor-Bearing Mice.
M. Gil, M. Bieniasz, A. Wierzbicki, B. J. Bambach, H. Rokita, and D. Kozbor (2009)
J. Immunol.
183, 6808-6818
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