Linked Life Data

10415014

Source:http://linkedlifedata.com/resource/pubmed/id/10415014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-8-12
pubmed:abstractText
We investigated the expression and function of Fas on human thymocytes prepared from fetal and pediatric tissue specimens and from SCID-hu Thy/Liv grafts. Unlike mouse thymocytes, human thymocytes exhibited a pattern of Fas expression skewed to immature cells, in that the highest expression was seen on double negative thymocytes and on intrathymic T progenitor cells. Fas expression was intermediate on double positive human thymocytes, and low or negative on mature single positive CD4 and CD8 medullary thymocytes. In spite of this relatively abundant surface expression, cross-linking of Fas with agonist mAb was incapable of triggering an apoptotic signal in human thymocytes. Apoptotic signaling was not enhanced by treatment with cycloheximide, nor by restoring a cosignaling milieu by addition of thymic stromal cells. Mouse thymocytes were induced to apoptosis by cross-linked recombinant soluble human Fas ligand both in vitro and in vivo, though human thymocytes were also resistant to this mode of receptor ligation. Membrane-bound Fas ligand also induced apoptotic death in murine thymocytes but not in human thymocytes. Human thymocytes were as sensitive as Jurkat cells, however, to apoptosis induced by TNF-alpha, suggesting that these cells have a signaling defect before activation of the earliest caspases. These data demonstrate a durable and specific resistance of human thymocytes to apoptosis induced through Fas receptor engagement, and reveal significant species-specific differences in the biology of thymocyte-programmed cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1195-204
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10415014-Animals, pubmed-meshheading:10415014-Antibodies, Monoclonal, pubmed-meshheading:10415014-Antigens, CD95, pubmed-meshheading:10415014-Apoptosis, pubmed-meshheading:10415014-Cell Differentiation, pubmed-meshheading:10415014-Cell Membrane, pubmed-meshheading:10415014-Cells, Cultured, pubmed-meshheading:10415014-Child, pubmed-meshheading:10415014-Child, Preschool, pubmed-meshheading:10415014-Fas Ligand Protein, pubmed-meshheading:10415014-Fetus, pubmed-meshheading:10415014-Humans, pubmed-meshheading:10415014-Infant, pubmed-meshheading:10415014-Injections, Intravenous, pubmed-meshheading:10415014-Ligands, pubmed-meshheading:10415014-Membrane Glycoproteins, pubmed-meshheading:10415014-Mice, pubmed-meshheading:10415014-Mice, Inbred BALB C, pubmed-meshheading:10415014-Mice, Inbred C57BL, pubmed-meshheading:10415014-Mice, SCID, pubmed-meshheading:10415014-Recombinant Fusion Proteins, pubmed-meshheading:10415014-Signal Transduction, pubmed-meshheading:10415014-Solubility, pubmed-meshheading:10415014-T-Lymphocytes, pubmed-meshheading:10415014-Thymus Gland
pubmed:year
1999
pubmed:articleTitle
Fas is expressed early in human thymocyte development but does not transmit an apoptotic signal.
pubmed:affiliation
Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco 94141, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't