Source:http://linkedlifedata.com/resource/pubmed/id/12695117
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2003-4-15
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pubmed:abstractText |
During antigen presentation, CD4 functions to stabilize T cell receptor (TCR)-class II MHC interactions and coordinate Ag-induced T cell activation signals. These activation signals cause CD4 down-regulation, presumably acting to optimize T cell activation. We previously reported that oxidative stress interferes with activation-induced CD4 down-regulation in T cells. In this study, we have further investigated inhibition of CD4 down-regulation by oxidative stress and its role for T cell activation. A construct comprised of the mouse FcgammaRIIB extracellular domain and the transmembrane/cytoplasmic domains of human CD4 (FcgammaR/CD4) was expressed in a human T cell line. Oxidant actually potentiated down-regulation of the FcgammaR/CD4 chimera and induced Lck dissociation from both CD4 and FcgammaR/CD4, which is a crucial intracellular process for activation-induced CD4 down-regulation, suggesting a critical role of CD4 ectodomain in the inhibition of CD4 down-regulation by oxidative stress. Furthermore, insertion of CD4 D3-D4 membrane proximal extracellular region between FcgammaR extracellular domain and CD4 transmembrane/cytoplasmic domains in FcgammaR/CD4 chimera made this molecule behave like native CD4 molecule under oxidative stress condition. These data imply that the inhibitory effect of oxidative stress on CD4 down-regulation is executed via D3-D4 domain of CD4 ectodomain. As to its role for T cell activation, CD4 coaggregation with CD3 under the oxidative conditions enhanced activation signal induced by CD3 aggregation. Our results demonstrate that Ag-induced T cell activation which is normally concomitant with CD4 down-regulation may be disturbed through the aberrant regulation of CD4 expression by oxidative stress.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Fc gamma receptor IIB,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor-CD3 Complex, Antigen...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0161-5890
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
909-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12695117-Amino Acid Sequence,
pubmed-meshheading:12695117-Antigens, CD,
pubmed-meshheading:12695117-Antigens, CD4,
pubmed-meshheading:12695117-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12695117-Cells, Cultured,
pubmed-meshheading:12695117-Down-Regulation,
pubmed-meshheading:12695117-Humans,
pubmed-meshheading:12695117-Jurkat Cells,
pubmed-meshheading:12695117-Lymphocyte Activation,
pubmed-meshheading:12695117-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:12695117-Molecular Sequence Data,
pubmed-meshheading:12695117-Oxidants,
pubmed-meshheading:12695117-Oxidative Stress,
pubmed-meshheading:12695117-Phosphorylation,
pubmed-meshheading:12695117-Protein Kinase C,
pubmed-meshheading:12695117-Protein Structure, Tertiary,
pubmed-meshheading:12695117-Receptor-CD3 Complex, Antigen, T-Cell,
pubmed-meshheading:12695117-Receptors, IgG,
pubmed-meshheading:12695117-Recombinant Fusion Proteins,
pubmed-meshheading:12695117-Tyrosine
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pubmed:year |
2003
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pubmed:articleTitle |
Involvement of CD4 D3-D4 membrane proximal extracellular domain for the inhibitory effect of oxidative stress on activation-induced CD4 down-regulation and its possible role for T cell activation.
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pubmed:affiliation |
Department of Immunology and Immunopathology, Kagawa Medical University, 1750-1 Ikenobe, Miki, Kita-gun, 761-0793, Kagawa, Japan. immunol@kms.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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