rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
8
|
pubmed:dateCreated |
2004-10-7
|
pubmed:abstractText |
CD4+CD25+ regulatory T cells (Treg) acquire unique immunosuppressive properties while maintaining an anergy phenotype when activated in vitro under conditions that induce IL-2 production and proliferation in conventional CD4+ T cells. We investigated the mechanism underlying one component of this naturally anergic phenotype, the inability of the Treg cells to produce IL-2 following activation. Analysis of freshly isolated murine CD4+CD25+ Treg and conventional CD4+CD25- T cells following PMA/ionomycin stimulation demonstrated no differences in inducible AP-1 formation, an important transcriptional complex in regulating IL-2 gene expression. Although p38 MAPK and ERK1/2 protein kinases were phosphorylated with similar kinetics, we observed diminished activation of JNK in the CD4+CD25+ Treg cells. However, lentiviral-mediated reconstitution of the JNK pathway using a constitutively active construct did not overcome the block in IL-2 synthesis. Using a PCR-based chromatin accessibility assay we found that the minimal IL-2 promoter region of CD4+CD25+ Treg cells, unlike conventional CD4 T cells, did not undergo chromatin remodeling following stimulation, suggesting that the inability of CD4+CD25+ Treg cells to secrete IL-2 following activation is controlled at the chromatin level.
|
pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
0022-1767
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
173
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4994-5001
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:15470042-Animals,
pubmed-meshheading:15470042-Antigens, CD4,
pubmed-meshheading:15470042-Immune Tolerance,
pubmed-meshheading:15470042-Interleukin-2,
pubmed-meshheading:15470042-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15470042-Lymphocyte Activation,
pubmed-meshheading:15470042-Mice,
pubmed-meshheading:15470042-Mice, Inbred BALB C,
pubmed-meshheading:15470042-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15470042-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15470042-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15470042-Promoter Regions, Genetic,
pubmed-meshheading:15470042-Receptors, Interleukin-2,
pubmed-meshheading:15470042-Signal Transduction,
pubmed-meshheading:15470042-T-Lymphocytes,
pubmed-meshheading:15470042-Transcription Factor AP-1,
pubmed-meshheading:15470042-p38 Mitogen-Activated Protein Kinases
|
pubmed:year |
2004
|
pubmed:articleTitle |
Murine CD4+CD25+ regulatory T cells fail to undergo chromatin remodeling across the proximal promoter region of the IL-2 gene.
|
pubmed:affiliation |
Division of Immunology and Rheumatology, Department of Medicine, Stanford University, CA 94305, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|