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Science 299 (5609): 1033-1036

Copyright © 2003 by the American Association for the Advancement of Science

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, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of 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}

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   Abstract »    Full Text »    PDF »
The Pathogen Recognition Receptor NOD2 Regulates Human FOXP3+ T Cell Survival.
M. K. Rahman, E. H. Midtling, P. A. Svingen, Y. Xiong, M. P. Bell, J. Tung, T. Smyrk, L. J. Egan, and W. A. Faubion Jr. (2010)
J. Immunol. 184, 7247-7256
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Blockade of CCL1 Inhibits T Regulatory Cell Suppressive Function Enhancing Tumor Immunity without Affecting T Effector Responses.
D. B. Hoelzinger, S. E. Smith, N. Mirza, A. L. Dominguez, S. Z. Manrique, and J. Lustgarten (2010)
J. Immunol. 184, 6833-6842
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Oral Vaccination with Attenuated Salmonella enterica Strains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses.
J.-Z. Meng, Y.-J. Dong, H. Huang, S. Li, Y. Zhong, S.-L. Liu, and Y.-D. Wang (2010)
Clin. Vaccine Immunol. 17, 889-894
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APC Activation by IFN-{alpha} Decreases Regulatory T Cell and Enhances Th Cell Functions.
L. Pace, S. Vitale, B. Dettori, C. Palombi, V. La Sorsa, F. Belardelli, E. Proietti, and G. Doria (2010)
J. Immunol. 184, 5969-5979
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RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter.
S. Burgler, P. Y. Mantel, C. Bassin, N. Ouaked, C. A. Akdis, and C. B. Schmidt-Weber (2010)
J. Immunol. 184, 6161-6169
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Differential but Direct Abolishment of Human Regulatory T Cell Suppressive Capacity by Various TLR2 Ligands.
H. H. Oberg, T. T. H. Ly, S. Ussat, T. Meyer, D. Kabelitz, and D. Wesch (2010)
J. Immunol. 184, 4733-4740
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Regulatory T Cells Inhibit T Cell Proliferation and Decrease Demyelination in Mice Chronically Infected with a Coronavirus.
K. Trandem, D. Anghelina, J. Zhao, and S. Perlman (2010)
J. Immunol. 184, 4391-4400
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Intra-tumoral dendritic cells increase efficacy of peripheral vaccination by modulation of glioma microenvironment.
S. Pellegatta, P. L. Poliani, E. Stucchi, D. Corno, C. A. Colombo, F. Orzan, M. Ravanini, and G. Finocchiaro (2010)
Neuro Oncology 12, 377-388
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Toll-like Receptor 3-Mediated Suppression of TRAMP Prostate Cancer Shows the Critical Role of Type I Interferons in Tumor Immune Surveillance.
A. I. Chin, A. K. Miyahira, A. Covarrubias, J. Teague, B. Guo, P. W. Dempsey, and G. Cheng (2010)
Cancer Res. 70, 2595-2603
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Ischemic Injury Enhances Dendritic Cell Immunogenicity via TLR4 and NF-{kappa}B Activation.
M. Jurewicz, A. Takakura, A. Augello, S. M. Naini, T. Ichimura, K. Zandi-Nejad, and R. Abdi (2010)
J. Immunol. 184, 2939-2948
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