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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1997-6-19
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pubmed:abstractText |
Collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis, is induced in DBA/1 (H-2q) mice following immunization with type II collagen (CII) in CFA. Since we have previously shown that IFN-gamma exerts a biphasic effect during the evolution of CIA in DBA/1 mice, we analyzed the development of this disease in mice with a disruption of the IFN-gamma receptor gene (IFN-gammaR(0/0)). Mutant mice were interbred with the DBA/1 strain to yield IFN-gammaR(0/0) mice expressing the H-2q haplotype. In three consecutive experiments, IFN-gammaR(0/0) male mice were found to exhibit severe clinical and histologic arthritis with an average incidence of 88.5 vs 94.1% for the wild DBA/1 strain. Notably, onset of clinical symptoms occurred significantly earlier than in DBA/1 mice. Although of a lower magnitude than in males, CIA also developed early in IFN-gammaR(0/0) female mice and with higher clinical severity than in control DBA/1 females. Immunization of knockout mice with CII resulted in the generation of CII-specific T cells belonging to the Th1 phenotype that recognize the same immunodominant peptides as do DBA/1 mice. CIA in IFN-gammaR(0/0) mice was associated with a down-regulation of the CII-specific IgG response, and this impairment was essentially due to a strong reduction of Abs of the IgG2a isotype. Taken together, our findings provide evidence that IFN-gammaR deficiency in DBA/1 mice leads to the occurrence of severe CIA with an accelerated onset compared with that in wild-type mice, indicating that the proinflammatory action of IFN-gamma has been bypassed in the IFN-gammaR(0/0) mice.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
158
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5501-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9164973-Animals,
pubmed-meshheading:9164973-Arthritis,
pubmed-meshheading:9164973-Collagen,
pubmed-meshheading:9164973-Disease Susceptibility,
pubmed-meshheading:9164973-Female,
pubmed-meshheading:9164973-Immunoglobulin G,
pubmed-meshheading:9164973-Male,
pubmed-meshheading:9164973-Mice,
pubmed-meshheading:9164973-Mice, Mutant Strains,
pubmed-meshheading:9164973-Receptors, Interferon,
pubmed-meshheading:9164973-Th1 Cells
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pubmed:year |
1997
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pubmed:articleTitle |
High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors.
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pubmed:affiliation |
National Institute of Health and Medical Research (INSERM), Unit 283, René Descartes University, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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