| pubmed-article:12209621 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12209621 | lifeskim:mentions | umls-concept:C0111208 | lld:lifeskim |
| pubmed-article:12209621 | lifeskim:mentions | umls-concept:C0425152 | lld:lifeskim |
| pubmed-article:12209621 | lifeskim:mentions | umls-concept:C1523116 | lld:lifeskim |
| pubmed-article:12209621 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:12209621 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:12209621 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:12209621 | pubmed:dateCreated | 2002-9-4 | lld:pubmed |
| pubmed-article:12209621 | pubmed:abstractText | CTLA-4 engagement inhibits TCR-dependent functions and CTLA-4(-/-) mice develop a lymphoproliferative disorder leading to early lethality. In vitro, ligation of CTLA-4 reduces TCR-mediated activation of NF-kappaB, a transcription factor implicated in promoting T cell survival and cytokine production. However, whether NF-kappaB inhibition downstream of CTLA-4 is necessary for down-regulation of T cell responses is not known. We hypothesized that signaling pathways that are antagonized when CTLA-4 is engaged should be augmented when CTLA-4 is absent and found thatspontaneous NF-kappaB activity was increased in T cells from CTLA-4(-/-) mice. To determine the importance of NF-kappaB inhibition upon CTLA-4 engagement in vivo, CTLA-4(-/-) mice were interbred with mice expressing a transdominant IkappaBalpha mutant under the control of the Lck promoter. The resulting mice had reduced spontaneous NF-kappaB activity in T cells,delayed mortality, and reduced leukocytic accumulation in spleen, lymph nodes, and exocrine pancreas as compared with CTLA-4(-/-) littermates. However, impaired NF-kappaB activation in T cells did not prevent the up-regulation of activation markers on T cells or the acquisition of effector cytokine production. Thus, impaired NF-kappaB activity in T cells prevents specific aspects of the CTLA-4(-/-) phenotype, suggesting that inhibition of NF-kappaB activation is one of the key biochemical events regulated by CTLA-4 ligation in vivo. | lld:pubmed |
| pubmed-article:12209621 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12209621 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12209621 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12209621 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:12209621 | pubmed:issn | 0014-2980 | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:ThompsonCraig... | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:BoothbyMarkM | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:HwangKwang... | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:AlegreMaria-L... | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:HarlinHelenaH | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:PaluckiDavid... | lld:pubmed |
| pubmed-article:12209621 | pubmed:author | pubmed-author:KimOliverO | lld:pubmed |
| pubmed-article:12209621 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12209621 | pubmed:volume | 32 | lld:pubmed |
| pubmed-article:12209621 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12209621 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12209621 | pubmed:pagination | 2095-104 | lld:pubmed |
| pubmed-article:12209621 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:12209621 | pubmed:meshHeading | pubmed-meshheading:12209621... | lld:pubmed |
| pubmed-article:12209621 | pubmed:meshHeading | pubmed-meshheading:12209621... | lld:pubmed |
| pubmed-article:12209621 | pubmed:meshHeading | pubmed-meshheading:12209621... | lld:pubmed |
| pubmed-article:12209621 | pubmed:meshHeading | pubmed-meshheading:12209621... | lld:pubmed |
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| pubmed-article:12209621 | pubmed:meshHeading | pubmed-meshheading:12209621... | lld:pubmed |
| pubmed-article:12209621 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12209621 | pubmed:articleTitle | CTLA-4 engagement regulates NF-kappaB activation in vivo. | lld:pubmed |
| pubmed-article:12209621 | pubmed:affiliation | Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, Ill 60637 USA. | lld:pubmed |
| pubmed-article:12209621 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12209621 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12209621 | lld:pubmed |
