| Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment. | |
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MedLine Citation:
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PMID: 15383577 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Corneal grafts were until recently considered entirely devoid of resident APCs, giving rise to the tenet that alloantigen recognition is mediated exclusively by the indirect (host APC-dependent) pathway. The recent discovery of a resident myeloid corneal dendritic cell population that is normally MHC class II(-) but can readily up-regulate class II expression during inflammation led us to hypothesize that under certain conditions the direct pathway of allosensitization becomes operative. To test this, corneal allotransplants were performed in either inflamed (high-risk (HR)) or uninflamed (low-risk (LR)) host beds in mice, and the frequencies of host T cells activated via the direct pathway were determined. We found that directly primed CD4(+) T cells were detected in the HR but not LR setting, and these cells displayed a clear Th1 phenotype by 2 wk after grafting. Moreover, the use of MHC class II knockout donor tissue led to significantly enhanced survival of HR but not LR allografts. Finally, we show that donor corneal APC demonstrate high expression of CD40, CD80, and CD86 costimulatory molecules when derived from HR but not LR grafts. These data are the first to report that a functional donor APC-dependent direct response is elicited in corneal transplant hosts when the graft bed is inflamed and underscore the relevance of the graft microenvironment in dictating the pathway of allosensitization. |
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Authors:
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Syed Huq; Ying Liu; Gilles Benichou; M Reza Dana |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 173 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-22 Completed Date: 2004-11-15 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4464-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Ophthalmology, Schepens Eye Research Institute, Boston, MA 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen-Presenting Cells / immunology, metabolism, pathology Antigens, CD / biosynthesis Antigens, CD40 / biosynthesis Antigens, CD80 / biosynthesis Antigens, CD86 CD4-Positive T-Lymphocytes / immunology, metabolism CD8-Positive T-Lymphocytes / immunology, metabolism Cornea / blood supply*, immunology*, pathology Corneal Transplantation / immunology*, pathology* Graft Survival / genetics, immunology Histocompatibility Antigens Class II / genetics Interferon-gamma / biosynthesis Interleukin-2 / biosynthesis Membrane Glycoproteins / biosynthesis Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Postoperative Complications / immunology, pathology Risk Factors Signal Transduction / genetics, immunology* Th1 Cells / immunology, metabolism Th2 Cells / immunology, metabolism Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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13310//PHS HHS; R01-12963//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, CD40; 0/Antigens, CD80; 0/Antigens, CD86; 0/Cd86 protein, mouse; 0/Histocompatibility Antigens Class II; 0/Interleukin-2; 0/Membrane Glycoproteins; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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