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rdf:type |
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lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0039194,
umls-concept:C0040648,
umls-concept:C0205263,
umls-concept:C0206120,
umls-concept:C0871261,
umls-concept:C1332714,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
12
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pubmed:dateCreated |
2004-12-8
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pubmed:abstractText |
Ag-specific immune tolerance results from the induction of cellular mechanisms that limit T cell responses to selective Ags. One of these mechanisms is characterized by attenuated proliferation and decreased IL-2 production in fully stimulated CD4(+) Th cells and is denoted T cell anergy. We report the identification of the early growth response gene (Egr-2; Krox-20), a zinc-finger transcription factor, as a key protein required for induction of anergy in cultured T cells. Gene array screening revealed high Egr-2 expression distinctly persists in anergized but not proliferating murine A.E7 T cells. In contrast, Egr-1, a related family member induced upon costimulation, displays little or no expression in the anergic state. IL-2-mediated abrogation of anergy causes rapid depletion of Egr-2 protein. Full stimulation of anergic A.E7 T cells fails to enhance IL-2 and Egr-1 expression, whereas Egr-2 expression is greatly increased. Silencing Egr-2 gene expression by small interfering RNA treatment of cultured A.E7 T cells before incubation with anti-CD3 alone prevents full induction of anergy. However, small interfering RNA-mediated depletion of Egr-2 5 days after anergy induction does not appear to abrogate hyporesponsiveness to stimulation. These data indicate that sustained Egr-2 expression is necessary to induce a full anergic state through the actions of genes regulated by this transcription factor.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Egr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7331-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15585857-Animals,
pubmed-meshheading:15585857-Antigens, CD28,
pubmed-meshheading:15585857-Antigens, CD3,
pubmed-meshheading:15585857-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15585857-Cell Line,
pubmed-meshheading:15585857-Cell Proliferation,
pubmed-meshheading:15585857-Clonal Anergy,
pubmed-meshheading:15585857-Clone Cells,
pubmed-meshheading:15585857-DNA-Binding Proteins,
pubmed-meshheading:15585857-Early Growth Response Protein 2,
pubmed-meshheading:15585857-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15585857-Gene Expression Regulation,
pubmed-meshheading:15585857-Gene Silencing,
pubmed-meshheading:15585857-Interleukin-2,
pubmed-meshheading:15585857-Lymphocyte Activation,
pubmed-meshheading:15585857-Mice,
pubmed-meshheading:15585857-Mice, Inbred C57BL,
pubmed-meshheading:15585857-Phosphorylation,
pubmed-meshheading:15585857-RNA, Small Interfering,
pubmed-meshheading:15585857-Receptors, Antigen, T-Cell,
pubmed-meshheading:15585857-Transcription Factors,
pubmed-meshheading:15585857-Up-Regulation,
pubmed-meshheading:15585857-Zinc Fingers
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pubmed:year |
2004
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pubmed:articleTitle |
Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cells.
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pubmed:affiliation |
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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