Document Detail


Local and systemic effects of co-stimulatory blockade using cytotoxic T lymphocyte antigen-4-immunoglobulin in dinitrofluorobenzene- and oxazolone-induced contact hypersensitivity in mice.
MedLine Citation:
PMID:  23286949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A D Christensen; S Skov; C Haase
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-03-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  220-30     Citation Subset:  IM    
Copyright Information:
© 2012 Novo Nordisk A/S Clinical and Experimental Immunology © 2012 British Society for Immunology.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Cytokines; 0/Immunoconjugates; 0/Inflammation Mediators; 15646-46-5/Oxazolone; 7D0YB67S97/abatacept; D241E059U6/Dinitrofluorobenzene
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