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PMID: 12532024 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.

Science (New York, N.Y.) ·Vol. 299 ·No. 5609 ·2003-02-14 ·Pages 1033-6

Pasare C, Medzhitov R

Abstract

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.

MeSH Terms

Adaptor Proteins, Signal Transducing Animals Antigens, CD/immunology,metabolism Antigens, Differentiation/metabolism Cells, Cultured Culture Media, Conditioned Dendritic Cells/immunology,metabolism Dinucleoside Phosphates/immunology Drosophila Proteins Immune Tolerance Immunization Interleukin-6/metabolism,physiology Lipopolysaccharides/immunology Lymphocyte Activation Membrane Glycoproteins/physiology Mice Mice, Inbred C57BL Myeloid Differentiation Factor 88 Ovalbumin/immunology Receptors, Cell Surface/physiology Receptors, Immunologic/metabolism Self Tolerance T-Lymphocytes/immunology T-Lymphocytes, Regulatory/immunology Toll-Like Receptors

Chemicals

Adaptor Proteins, Signal Transducing Antigens, CD Antigens, Differentiation Culture Media, Conditioned Dinucleoside Phosphates Drosophila Proteins Interleukin-6 Lipopolysaccharides Membrane Glycoproteins Myd88 protein, mouse Myeloid Differentiation Factor 88 Receptors, Cell Surface Receptors, Immunologic Toll-Like Receptors cytidylyl-3'-5'-guanosine Ovalbumin

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Pasare Chandrashekhar

Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

Medzhitov Ruslan

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1078231

Published

2003-02-14

Epub

2003-00-16

Pages

1033-6

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 12586934

External Links

PubMed source DOI: 10.1126/science.1078231 View journal details

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Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.

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