| pubmed-article:12110140 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12110140 | lifeskim:mentions | umls-concept:C1155065 | lld:lifeskim |
| pubmed-article:12110140 | lifeskim:mentions | umls-concept:C0021376 | lld:lifeskim |
| pubmed-article:12110140 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:12110140 | pubmed:dateCreated | 2002-7-11 | lld:pubmed |
| pubmed-article:12110140 | pubmed:abstractText | The strong association between specific alleles encoded within the MHC class II region and the development of rheumatoid arthritis (RA) has provided the best evidence to date that CD4+ T cells play a role in the pathogenesis of this chronic inflammatory disease. However, the unusual phenotype of synovial T cells, including their profound proliferative hyporesponsiveness to TCR ligation, has challenged the notion that T-cell effector responses are driven by cognate cartilage antigens in inflamed synovial joints. The hierarchy of T-cell dysfunction from peripheral blood to inflamed joint suggests that these defects are acquired through prolonged exposure to proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha. Indeed, there are now compelling data to suggest that chronic cytokine activation may contribute substantially to the phenotype and effector function of synovial T cells. Studies reveal that chronic exposure of T cells to TNF uncouples TCR signal transduction pathways by impairing the assembly and stability of the TCR/CD3 complex at the cell surface. Despite this membrane-proximal effect, TNF selectively uncouples downstream signalling pathways, as is shown by the dramatic suppression of calcium signalling responses, while Ras/ERK activation is spared. On the basis of these data, it is proposed that T-cell survival and effector responses are driven by antigen-independent, cytokine-dependent mechanisms, and that therapeutic strategies that seek to restore T-cell homeostasis rather than further depress T-cell function should be explored in the future. | lld:pubmed |
| pubmed-article:12110140 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12110140 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12110140 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12110140 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12110140 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12110140 | pubmed:issn | 1465-9905 | lld:pubmed |
| pubmed-article:12110140 | pubmed:author | pubmed-author:CopeAndrew... | lld:pubmed |
| pubmed-article:12110140 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12110140 | pubmed:volume | 4 Suppl 3 | lld:pubmed |
| pubmed-article:12110140 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12110140 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12110140 | pubmed:pagination | S197-211 | lld:pubmed |
| pubmed-article:12110140 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:meshHeading | pubmed-meshheading:12110140... | lld:pubmed |
| pubmed-article:12110140 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12110140 | pubmed:articleTitle | Studies of T-cell activation in chronic inflammation. | lld:pubmed |
| pubmed-article:12110140 | pubmed:affiliation | The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, London, UK. andrew.cope@ic.ac.uk | lld:pubmed |
| pubmed-article:12110140 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12110140 | pubmed:publicationType | Review | lld:pubmed |
| pubmed-article:12110140 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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