Linked Life Data

20147632

Source:http://linkedlifedata.com/resource/pubmed/id/20147632

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-3-4
pubmed:abstractText
Increased proportions of CD8 T lymphocytes lacking expression of the CD28 costimulatory receptor have been documented during both aging and chronic infection with HIV-1, and their abundance correlates with numerous deleterious clinical outcomes. CD28-negative cells also arise in cell cultures of CD8(+)CD28(+) following multiple rounds of Ag-driven proliferation, reaching the end stage of replicative senescence. The present study investigates the role of a second T cell costimulatory receptor component, adenosine deaminase (ADA), on the process of replicative senescence. We had previously reported that CD28 signaling is required for optimal telomerase upregulation. In this study, we show that the CD8(+)CD28(+) T lymphocytes that are ADA(+) have significantly greater telomerase activity than those that do not express ADA and that ADA is progressively lost as cultures progress to senescence. Because ADA converts adenosine to inosine, cells lacking this enzyme might be subject to prolonged exposure to adenosine, which has immunosuppressive effects. Indeed, we show that chronic exposure of CD8 T lymphocytes to exogenous adenosine accelerates the process of replicative senescence, causing a reduction in overall proliferative potential, reduced telomerase activity, and blunted IL-2 gene transcription. The loss of CD28 expression was accelerated, in part due to adenosine-induced increases in constitutive caspase-3, known to act on the CD28 promoter. These findings provide the first evidence for a role of ADA in modulating the process of replicative senescence and suggest that strategies to enhance this enzyme may lead to novel therapeutic approaches for pathologies associated with increases in senescent CD8 T lymphocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
184
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2847-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20147632-Adenosine, pubmed-meshheading:20147632-Adenosine Deaminase, pubmed-meshheading:20147632-Adenosine Deaminase Inhibitors, pubmed-meshheading:20147632-Antigens, CD28, pubmed-meshheading:20147632-Antigens, CD8, pubmed-meshheading:20147632-CD8-Positive T-Lymphocytes, pubmed-meshheading:20147632-Cell Aging, pubmed-meshheading:20147632-Cell Division, pubmed-meshheading:20147632-Cell Proliferation, pubmed-meshheading:20147632-Cells, Cultured, pubmed-meshheading:20147632-Down-Regulation, pubmed-meshheading:20147632-Enzyme Activation, pubmed-meshheading:20147632-HIV Infections, pubmed-meshheading:20147632-Humans, pubmed-meshheading:20147632-Immunophenotyping, pubmed-meshheading:20147632-Lymphocyte Activation, pubmed-meshheading:20147632-Telomerase, pubmed-meshheading:20147632-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Adenosine deaminase modulation of telomerase activity and replicative senescence in human CD8 T lymphocytes.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural