Source:http://linkedlifedata.com/resource/pubmed/id/17028587
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2006-10-20
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pubmed:abstractText |
Anergic T cells have altered diacylglycerol metabolism, but whether that altered metabolism has a causative function in the induction of T cell anergy is not apparent. To test the importance of diacylglycerol metabolism in T cell anergy, we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate diacylglycerol-dependent signaling. Overexpression of DGK-alpha resulted in a defect in T cell receptor signaling that is characteristic of anergy. We generated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction was impaired in DGK-alpha-deficient mice. When stimulated in anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2. Pharmacological inhibition of DGK-alpha activity in DGK-zeta-deficient T cells that received an anergizing stimulus proliferated similarly to wild-type T cells that received CD28 costimulation and prevented anergy induction. Our findings suggest that regulation of diacylglycerol metabolism is critical in determining whether activation or anergy ensues after T cell receptor stimulation.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1529-2908
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1174-81
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:17028587-Animals,
pubmed-meshheading:17028587-Clonal Anergy,
pubmed-meshheading:17028587-Diacylglycerol Kinase,
pubmed-meshheading:17028587-Diglycerides,
pubmed-meshheading:17028587-Lymphocyte Activation,
pubmed-meshheading:17028587-Mice,
pubmed-meshheading:17028587-Mice, Knockout,
pubmed-meshheading:17028587-Receptors, Antigen, T-Cell,
pubmed-meshheading:17028587-T-Lymphocytes
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pubmed:year |
2006
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pubmed:articleTitle |
Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.
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pubmed:affiliation |
Signal Transduction Program, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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