Statements in which the resource exists as a subject.
PredicateObject
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
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