Source:http://linkedlifedata.com/resource/pubmed/id/11823542
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2002-2-1
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| pubmed:abstractText |
Short-term combination therapy with the costimulatory antagonists CTLA4Ig and anti-CD40 ligand induces prolonged suppression of disease onset in New Zealand Black/New Zealand White F(1) systemic lupus erythematosus-prone mice. To determine the mechanism for this effect, 20- to 22-wk-old New Zealand Black/New Zealand White F(1) mice were treated with six doses each of CTLA4Ig and anti-CD40 ligand Ab over 2 wk. Combination-treated mice, but not mice treated with either agent alone, had prolonged survival and the production of pathogenic IgG anti-dsDNA Ab was suppressed. Twenty weeks after completion of treatment the frequency of activated B cells producing anti-dsDNA Ab was decreased, and the abnormal transition of T cells from the naive to the memory compartment was blocked. Combination treatment partially suppressed class switching and decreased the frequency of somatic mutations in the V(H)BW-16 gene, which is expressed by pathogenic anti-DNA Abs. Treated mice were still able to respond to the hapten oxazolone when it was given 8 wk after treatment initiation, and they mounted a somatically mutated IgG anti-oxazolone response that was noncross-reactive with dsDNA. Fifty to 60% of previously treated mice, but only 14% of previously untreated mice, responded within 2-3 wk to a second course of therapy given at the onset of fixed proteinuria and remained well for a further 3-4 mo. Although this treatment had no immediate effect on serum anti-dsDNA Abs or on the abnormal T cell activation observed in sick mice, 25% of treated mice lived for >18 mo compared with 5% of untreated controls. These results suggest that the effect of costimulatory blockade in remission induction must be mediated by a different mechanism than is demonstrated in the disease prevention studies.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Antinuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazolone,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
168
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2046-53
|
| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:11823542-Amino Acid Sequence,
pubmed-meshheading:11823542-Animals,
pubmed-meshheading:11823542-Antibodies,
pubmed-meshheading:11823542-Antibodies, Antinuclear,
pubmed-meshheading:11823542-Antigens, CD,
pubmed-meshheading:11823542-Antigens, Differentiation,
pubmed-meshheading:11823542-B-Lymphocytes,
pubmed-meshheading:11823542-CD40 Ligand,
pubmed-meshheading:11823542-CTLA-4 Antigen,
pubmed-meshheading:11823542-DNA,
pubmed-meshheading:11823542-Hybridomas,
pubmed-meshheading:11823542-Immunoconjugates,
pubmed-meshheading:11823542-Immunoglobulin Class Switching,
pubmed-meshheading:11823542-Immunosuppressive Agents,
pubmed-meshheading:11823542-Kinetics,
pubmed-meshheading:11823542-Lupus Erythematosus, Systemic,
pubmed-meshheading:11823542-Mice,
pubmed-meshheading:11823542-Mice, Inbred NZB,
pubmed-meshheading:11823542-Molecular Sequence Data,
pubmed-meshheading:11823542-Mutation,
pubmed-meshheading:11823542-Oxazolone,
pubmed-meshheading:11823542-Recombinant Fusion Proteins,
pubmed-meshheading:11823542-Spleen,
pubmed-meshheading:11823542-Treatment Outcome
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| pubmed:year |
2002
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| pubmed:articleTitle |
Mechanism of action of combined short-term CTLA4Ig and anti-CD40 ligand in murine systemic lupus erythematosus.
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| pubmed:affiliation |
Departments of. Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
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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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