Linked Life Data

1535086

Source:http://linkedlifedata.com/resource/pubmed/id/1535086

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-7-21
pubmed:abstractText
We previously demonstrated that long term treatment of the Ag-specific CD4+ T cell clone P28D with soluble HIV envelope glycoprotein gp120 results in a marked impairment of CD3/TCR-mediated responses. In this report, to further understand these inhibitory effects, the binding properties and internalization of gp120 have been investigated, in parallel with functional studies, in long term incubations of P28D cells with gp120. Immunofluorescence studies show that surface-bound gp120 level is maximal within 1 h of incubation at 37 degrees C and then gradually decreases. This decrease is accompanied by a progressive down-modulation of membrane CD4 (30-35% loss over a 18-h incubation period) without concomitant alteration of the CD4 mRNA steady-state level. Similar experiments performed with 125I-labeled gp120 demonstrate that the glycoprotein is progressively internalized (up to 35% internalized material after 18 h) and that it accumulates inside the cells. Confocal microscopy studies show that internalized gp120 is concentrated in localized intracellular compartments. CD4 also accumulates in compartments with a similar localization and is stained with mAb OKT4 but not with mAb OKT4a. Concomitantly to internalization of gp120 and disappearance of membrane CD4, a correlated loss of the CD4-associated tyrosine kinase p56lck is evidenced. Interestingly, a progressive impairment of the P28D responses to specific Ag or to anti-CD3 mAb is also observed. Inhibitions of T cell proliferation increase with the degree of both CD4 and p56lck down-modulation. Removal of exogenous gp120 results in a rapid and spontaneous release of internalized gp120 into a degraded form. A progressive restoration of CD4 and p56lck levels is also noticed. In parallel, CD3/TCR-mediated responses of clone P28D are fully recovered. Altogether, our results suggest that HIV-1 glycoprotein gp120 is able to down-modulate membrane CD4 presumably by a cointernalization process and to further down-modulate the associated p56lck. This dual phenomenon is presumably involved in the direct immunosuppressive effect of gp120 on the CD3/TCR-mediated activation pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-94
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:1535086-Antigens, CD3, pubmed-meshheading:1535086-Antigens, CD4, pubmed-meshheading:1535086-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:1535086-Cell Compartmentation, pubmed-meshheading:1535086-Cell Line, pubmed-meshheading:1535086-Cell Membrane, pubmed-meshheading:1535086-Down-Regulation, pubmed-meshheading:1535086-Endocytosis, pubmed-meshheading:1535086-Fluorescent Antibody Technique, pubmed-meshheading:1535086-HIV Envelope Protein gp120, pubmed-meshheading:1535086-Humans, pubmed-meshheading:1535086-Kinetics, pubmed-meshheading:1535086-Lymphocyte Activation, pubmed-meshheading:1535086-Lymphocyte Specific Protein Tyrosine Kinase p56(lck), pubmed-meshheading:1535086-Protein-Tyrosine Kinases, pubmed-meshheading:1535086-Receptors, Antigen, T-Cell, pubmed-meshheading:1535086-Signal Transduction, pubmed-meshheading:1535086-T-Lymphocytes
pubmed:year
1992
pubmed:articleTitle
Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation.
pubmed:affiliation
Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS URA 625, CERVI, Paris, France.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't