Document Detail

Connecting the mechanisms of T-cell regulation: dendritic cells as the missing link.
MedLine Citation:
PMID:  20636819     Owner:  NLM     Status:  MEDLINE    
A variety of different molecular mechanisms have been proposed to explain the suppressive action of regulatory T cells, including the production of anti-inflammatory cytokines, negative costimulatory ligands, indoleamine 2,3-dioxygenase-mediated tryptophan catabolism, CD73-mediated adenosine generation, and downregulation of antigen-presenting cells. Until now it has been unclear how important each of these different mechanisms might be and how they are coordinated. In this review, we examine the hypothesis that it is the interaction between regulatory T cells and dendritic cells that creates a local microenvironment depleted of essential amino acids and rich in adenosine that leads to the amplification of a range of different tolerogenic signals. These signals are all eventually integrated by mammalian target of rapamycin inhibition, which enables the induction of new forkhead box protein 3-expressing Tregs. If correct, this provides a molecular explanation for the in vivo phenomena of linked suppression and infectious tolerance.
Stephen P Cobbold; Elizabeth Adams; Kathleen F Nolan; Frederico S Regateiro; Herman Waldmann
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  236     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-10-29     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  203-18     Citation Subset:  IM    
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MeSH Terms
Antigen-Presenting Cells / immunology,  metabolism
Cell Communication / immunology*
Dendritic Cells / immunology*
Forkhead Transcription Factors / metabolism
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
Models, Immunological
Signal Transduction / immunology*
T-Lymphocytes, Regulatory / immunology*,  metabolism
Grant Support
G1000215//Medical Research Council
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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