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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1993-2-8
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pubmed:abstractText |
We have recently shown that activation of T cells causes structural changes in the interleukin-7 receptor (IL-7R) (Foxwell et al. Int. Immunol. 1992, 4: 277). Unactivated cells expressed a receptor characterized as a cross-linked protein of 107-kDa whereas activated cells had reduced levels of this 107-kDa complex and now express a major cross-linked product of 93 kDa. These changes in receptor expression were concomitant with the acquisition of IL-7 growth responsiveness by activated T cells. In this study, the effect of the potent immunosuppressive agents cyclosporin A and FK506 on the activation-induced responsiveness to IL-7-driven proliferation and the concomitant changes in receptor structure have been investigated. Cyclosporin A and FK506 suppressed the expression of the 93-kDa complex and the loss of the 107-kDa complex on activated cells. The presence of exogenous IL-7 inhibited the effects of the drugs on IL-7R structure, allowing expression of the 93-kDa complex. Expression of the 93-kDa complex could also be induced either by ionomycin or phorbol esters. As observed for other T cell activation parameters, only those which induced a calcium signal (ionomycin) but not protein kinase C (phorbol esters) were sensitive to the drugs. In all studies, the expression of the 93-kDa complex correlated with the ability of cells to proliferate to IL-7, and thus these results further support the hypothesis that the 93-kDa form of the IL-7R is required to transmit the cytokine's growth signal. Moreover, these data suggest that activation-induced transcriptional events are required for the expression of the 93-kDa complex and the down-regulation of the 107-kDa complex. As reported for IL-2R and IL-4R, our data also show that the expression of another T cell growth factor receptor is sensitive to the effects of cyclosporin A and FK506. These observations also have important implications for reported cyclosporin A effects on the thymus where IL-7 can act as a growth factor for thymocytes.
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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/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0014-2980
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
85-9
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:7678231-Cells, Cultured,
pubmed-meshheading:7678231-Cyclosporine,
pubmed-meshheading:7678231-Humans,
pubmed-meshheading:7678231-Interleukin-7,
pubmed-meshheading:7678231-Lymphocyte Activation,
pubmed-meshheading:7678231-Receptors, Immunologic,
pubmed-meshheading:7678231-Receptors, Interleukin-7,
pubmed-meshheading:7678231-T-Lymphocytes,
pubmed-meshheading:7678231-Tacrolimus
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pubmed:year |
1993
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pubmed:articleTitle |
Inhibition of activation-induced changes in the structure of the T cell interleukin-7 receptor by cyclosporin A and FK506.
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pubmed:affiliation |
Kennedy Institute for Rheumatology-Sunley Division, Hammersmith, London, GB.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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