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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}yale.edu



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R. Galli, D. Starace, R. Busa, D. F. Angelini, A. Paone, P. De Cesaris, A. Filippini, C. Sette, L. Battistini, E. Ziparo, et al. (2010)
J. Immunol. 184, 6658-6669
   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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »

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