Linked Life Data

12695117

Source:http://linkedlifedata.com/resource/pubmed/id/12695117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-4-15
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
909-21
pubmed:dateRevised
2009-11-19
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
pubmed:year
2003
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.
pubmed:affiliation
Department of Immunology and Immunopathology, Kagawa Medical University, 1750-1 Ikenobe, Miki, Kita-gun, 761-0793, Kagawa, Japan. immunol@kms.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't