Document Detail


Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression.
MedLine Citation:
PMID:  16482510     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-gamma and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.
Authors:
Sven C Beutelspacher; Radhakrishna Pillai; Martin P Watson; Peng H Tan; Julia Tsang; Myra O McClure; Andrew J T George; Daniel F P Larkin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  36     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-08     Completed Date:  2006-04-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  690-700     Citation Subset:  IM    
Affiliation:
Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Transformed
Cell Proliferation
Corneal Transplantation / immunology*
Endothelium, Corneal / enzymology,  immunology*
Female
Gene Expression Regulation, Enzymologic / genetics,  immunology*
Gene Transfer Techniques
Graft Rejection / enzymology,  genetics,  immunology*
Graft Survival / genetics,  immunology*
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors,  genetics,  immunology*
Interferon-gamma / immunology
Mice
Mice, Inbred BALB C
T-Lymphocytes / immunology
Transplantation, Homologous
Tumor Necrosis Factor-alpha / immunology
Up-Regulation / genetics,  immunology
Grant Support
ID/Acronym/Agency:
071527//Wellcome Trust
Chemical
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma; EC 1.13.11.42/Indoleamine-Pyrrole 2,3,-Dioxygenase

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


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