Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/8370
Full metadata record
DC FieldValueLanguage
dc.contributor.authorGermain, C-
dc.contributor.authorFu, H-
dc.contributor.authorLarkin, DFP-
dc.contributor.authorGeorge, AJT-
dc.date.accessioned2014-05-06T09:27:32Z-
dc.date.available2014-05-06T09:27:32Z-
dc.date.issued2011-
dc.identifier.citationInvestigative Ophthalmology & Visual Science, 52(5), 2640 - 2648, 2011en_US
dc.identifier.issn0146-0404-
dc.identifier.urihttp://www.iovs.org/content/52/5/2640en
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/8370-
dc.descriptionCopyright © 2011 Association for Research in Vision and Ophthalmology. This article is available open access through the publisher’s website at the link below.en_US
dc.description.abstractPurpose. IDO (indoleamine 2,3-dioxygenase) modulates the immune response by depletion of the essential amino acid tryptophan, and IDO overexpression has been shown to prolong corneal allograft survival. This study was conducted to examine the effect of kynurenines, the products of tryptophan breakdown and known to act directly on T lymphocytes, on corneal graft survival. Methods. The effects of kynurenines on T-cell proliferation and death, T-regulatory-cell development, and dendritic cell function, phenotype, and viability were analyzed in vitro. The effect of topical and systemic administration of 3-hydroxykynurenine (3HK) on orthotopic murine corneal allograft survival was examined. Results. T-lymphocyte proliferation was inhibited by two of the four different kynurenines: 3HK and 3-hydroxyanthranilic acid (3HAA). This effect was accompanied by significant T-cell death. Neither 3HK nor 3HAA altered dendritic cell function, nor did they induce apoptosis or pathogenicity to corneal endothelial cells. Administration of systemic and topical 3HK to mice receiving a fully mismatched corneal graft resulted in significant prolongation of graft survival (median survival of control grafts, 12 days; of treated, 19 and 15 days, respectively; P < 0.0003). While systemic administration of 3HK was associated with a significant depletion of CD4+ T, CD8+ T, and B lymphocytes in peripheral blood, no depletion was found after topical administration. Conclusions. The production of kynurenines, in particular 3HK and 3HAA, may be one mechanism (in addition to tryptophan depletion) by which IDO prolongs graft survival. These molecules have potential as specific agents for preventing allograft rejection in patients at high rejection risk.en_US
dc.description.sponsorshipFight for Sight and the Wellcome Trust.en_US
dc.languageEnglish-
dc.language.isoenen_US
dc.publisherAssociation for Research in Vision and Ophthalmologyen_US
dc.title3-hydroxykynurenine suppresses CD4+ T-cell proliferation, induces T-regulatory-cell development, and prolongs corneal allograft survivalen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1167/iovs.10-5793-
Appears in Collections:Biological Sciences
Publications
Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
Notice.pdf43.04 kBAdobe PDFView/Open


Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.