| Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression. | |
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MedLine Citation:
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PMID: 16482510 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 36 ISSN: 0014-2980 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-03-08 Completed Date: 2006-04-13 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 690-700 Citation Subset: IM |
Affiliation:
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Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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071527//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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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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