Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-5-9
pubmed:abstractText
Optimal CD4+ T cell activation requires the cooperation of multiple signaling pathways coupled to the TCR-CD3 complex and to the CD28 costimulatory molecule. In this study, we have investigated the expression of surface CXC chemokine receptor 4 (CXCR4) in enriched populations of CD4+ T PBL, stimulated with anti-CD3 and anti-CD28 mAbs, immobilized on plastic. Anti-CD3 alone induced a progressive down-regulation of surface CXCR4, accompanied by a significant decline in the entry of the HXB2 T cell line-tropic (X4-tropic) HIV-1 clone in CD4+ T cells. Of note, this effect was strictly dependent on the presence in culture of CD14+ monocytes. On the other hand, anti-CD28 alone induced a small but reproducible increase in the expression of surface CXCR4 as well as in the entry of HXB2 HIV-1 clone in resting CD4+ T cells. When the two mAbs were used in combination, anti-CD28 potently synergized with anti-CD3 in inducing the expression of CD69 activation marker and stimulating the proliferation of CD4+ T cells. On the other hand, anti-CD28 counteracted the CXCR4 down-modulation induced by anti-CD3. The latter effect was particularly evident when anti-CD28 was associated to suboptimal concentrations of anti-CD3. Because CXCR4 is the major coreceptor for the highly cytopathic X4-tropic HIV-1 strains, which preferentially replicate in proliferating CD4+ T cells, the ability of anti-CD28 to up-regulate the surface expression of CXCR4 in both resting and activated CD4+ T cells provides one relevant mechanism for the progression of HIV-1 disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4018-24
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10754293-Adult, pubmed-meshheading:10754293-Antibodies, Monoclonal, pubmed-meshheading:10754293-Antigens, CD14, pubmed-meshheading:10754293-Antigens, CD28, pubmed-meshheading:10754293-Antigens, CD3, pubmed-meshheading:10754293-CD4-Positive T-Lymphocytes, pubmed-meshheading:10754293-Cell Membrane, pubmed-meshheading:10754293-Cells, Cultured, pubmed-meshheading:10754293-Dose-Response Relationship, Immunologic, pubmed-meshheading:10754293-Down-Regulation, pubmed-meshheading:10754293-Extracellular Space, pubmed-meshheading:10754293-Gene Products, tat, pubmed-meshheading:10754293-HIV-1, pubmed-meshheading:10754293-Humans, pubmed-meshheading:10754293-Interphase, pubmed-meshheading:10754293-Monocytes, pubmed-meshheading:10754293-Receptors, CCR5, pubmed-meshheading:10754293-Receptors, CXCR4, pubmed-meshheading:10754293-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2000
pubmed:articleTitle
Engagement of CD28 modulates CXC chemokine receptor 4 surface expression in both resting and CD3-stimulated CD4+ T cells.
pubmed:affiliation
Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA. secchier@umbi.umd.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't