Source:http://linkedlifedata.com/resource/pubmed/id/11204564
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-2-1
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| pubmed:abstractText |
Mice genetically deficient in factor VII (fVIII) are a model of hemophilia A. As a first step to reproduce in this mouse model what occurs over time in hemophilia A patients treated with human fVIII (hfVIII), we have investigated the time course and the characteristics of their immune response to hfVIII, after multiple intravenous injections. Anti-hfVIII antibodies appeared after four to five injections. They were IgG1 and to a lesser extent IgG2, indicating that they were induced by both Th2 and Th1 cells. Inhibitors appeared after six injections. CD4+ enriched splenocytes from hfVIII-treated mice proliferated in response to fVIII and secreted IL-10: in a few mice they secreted also IFN-gamma and in one mouse IL-4, but never IL-2. A hfVIII-specific T cell line derived from hfVIII-treated mice secreted both IL-4 and IFN-gamma, suggesting that it included both Th1 and Th2 cells. CD4+ enriched splenocytes of hfIII-treated mice recognized all hfVIII domains. Thus, hemophilic mice develop an immune response to hfVIII administered intravenously similar to that of hemophilia A patients. Their anti-hfVIII antibodies can be inhibitors and belong to IgG subclasses homologous to those of inhibitors in hemophilic patients; their anti-hfVIII CD4+ cells recognize a complex repertoire and both Th1 and Th2 cytokines, and especially IL-10, may drive the antibody synthesis.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIII,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0340-6245
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
85
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
125-33
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11204564-Animals,
pubmed-meshheading:11204564-Antibodies,
pubmed-meshheading:11204564-Antibody-Producing Cells,
pubmed-meshheading:11204564-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11204564-Cell Division,
pubmed-meshheading:11204564-Cytokines,
pubmed-meshheading:11204564-Disease Models, Animal,
pubmed-meshheading:11204564-Epitopes,
pubmed-meshheading:11204564-Factor VIII,
pubmed-meshheading:11204564-Hemophilia A,
pubmed-meshheading:11204564-Humans,
pubmed-meshheading:11204564-Immunoglobulin G,
pubmed-meshheading:11204564-Injections, Intravenous,
pubmed-meshheading:11204564-Interleukin-10,
pubmed-meshheading:11204564-Mice,
pubmed-meshheading:11204564-Mice, Mutant Strains,
pubmed-meshheading:11204564-Spleen,
pubmed-meshheading:11204564-Time Factors
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| pubmed:year |
2001
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| pubmed:articleTitle |
Mechanism of the immune response to human factor VIII in murine hemophilia A.
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| pubmed:affiliation |
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis-St Paul, 55108, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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