| Local and systemic effects of co-stimulatory blockade using cytotoxic T lymphocyte antigen-4-immunoglobulin in dinitrofluorobenzene- and oxazolone-induced contact hypersensitivity in mice. | |
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MedLine Citation:
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PMID: 23286949 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)-immunoglobulin (Ig) has immunosuppressive properties both in vivo and in vitro, but much is still unknown about the mechanisms by which CTLA-4-Ig exerts its immunosuppressive activities in vivo. The aim of this study was to investigate the effect of CTLA-4-Ig in a mouse model of contact hypersensitivity (CHS). The inflammatory response in the presence or absence of CTLA-4-Ig was evaluated by measuring the increase in ear thickness in sensitized animals after challenge. We observed a dose-dependent suppression of the ear swelling in both dinitrofluorobenzene (DNFB)- and oxazolone-induced CHS. The suppressive effect was still present 3 weeks after administration, even in the absence of circulating levels of CTLA-4-Ig. It was further shown that CTLA-4-Ig inhibits activation of T cells in the draining lymph node after sensitization and affects the maturation level of both dendritic cells and B cells. Furthermore, CTLA-4-Ig reduces infiltration of activated CD8(+) T cells into the inflamed ear tissue and suppresses both local and systemic inflammation, as illustrated by reduced expression of cytokines and chemokines in the inflamed ear and a reduced level of acute-phase proteins in circulation. Finally, our results suggest that CTLA-4-Ig has a mainly immunosuppressive effect during the sensitization phase. We conclude that CTLA-4-Ig induces long-term immunosuppression of both DNFB- and oxazolone-induced inflammation and our data are the first to compare the effect of this compound in both DNFB- and oxazolone-induced CHS and to show that CTLA-4-Ig exerts an immunosuppressive effect on both local and systemic inflammatory mediators which is mediated principally during the sensitization phase. |
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Authors:
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A D Christensen; S Skov; C Haase |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 171 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-04 Completed Date: 2013-03-12 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 220-30 Citation Subset: IM |
Copyright Information:
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© 2012 Novo Nordisk A/S Clinical and Experimental Immunology © 2012 British Society for Immunology. |
Affiliation:
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Experimental Immunology Group, Department of Immunopharmacology, Novo Nordisk A/S, Måløv, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Cytokines / metabolism Dermatitis, Contact / drug therapy*, immunology Dinitrofluorobenzene / immunology Disease Models, Animal Female Humans Immune Tolerance Immunization Immunoconjugates / administration & dosage* Immunotherapy / methods* Inflammation Mediators / metabolism Mice Mice, Inbred BALB C Oxazolone / immunology Protein Binding / drug effects Receptor Cross-Talk |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Immunoconjugates; 0/Inflammation Mediators; 0/abatacept; 15646-46-5/Oxazolone; 70-34-8/Dinitrofluorobenzene |
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