Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-8-7
pubmed:abstractText
Glucocorticoids, administered in pharmacological doses, potently modulate immune system function and are a mainstay therapy for many common human diseases. Physiologic production of glucocorticoids may play a role in optimization of the immune repertoire both centrally and peripherally. Possible effects include alteration of lymphocyte development and down-regulation of cytokine responses, but essential roles remain unclear. To determine the part that endogenous glucocorticoids play in thymocyte development, we used fetal liver from mice lacking the glucocorticoid receptor GRko for immunological reconstitution of lethally irradiated wild-type (WT) mice. We find normal numbers and subset distribution of GRko thymocytes. GRko thymocytes also exhibit similar sensitivity to apoptosis induced by activating anti-CD3epsilon Ab as WT thymocytes in vitro. Surprisingly, GRko thymocytes are significantly more resistant than WT thymocytes to anti-CD3epsilon-mediated thymocyte apoptosis in vivo. Consistent with this finding, in vivo TCR complex activation induces sustained high levels of glucocorticoids that correlate strongly with thymocyte apoptosis in WT mice. We find that while direct engagement of the TCR complex may cause death of a subset of thymocytes, glucocorticoids are required for deletion of the majority of thymocytes. Thus, TCR stimulation by Ab administration may more accurately reflect polyclonal T cell activation than negative selection in vivo.
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
15
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1837-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12165507-Animals, pubmed-meshheading:12165507-Animals, Newborn, pubmed-meshheading:12165507-Antibodies, pubmed-meshheading:12165507-Antigens, CD3, pubmed-meshheading:12165507-Apoptosis, pubmed-meshheading:12165507-Corticosterone, pubmed-meshheading:12165507-Dexamethasone, pubmed-meshheading:12165507-Female, pubmed-meshheading:12165507-Fetus, pubmed-meshheading:12165507-Glucocorticoids, pubmed-meshheading:12165507-Humans, pubmed-meshheading:12165507-Liver, pubmed-meshheading:12165507-Lung, pubmed-meshheading:12165507-Lymphocyte Activation, pubmed-meshheading:12165507-Mice, pubmed-meshheading:12165507-Mice, Inbred C57BL, pubmed-meshheading:12165507-Mice, Knockout, pubmed-meshheading:12165507-Receptors, Antigen, T-Cell, pubmed-meshheading:12165507-Receptors, Glucocorticoid, pubmed-meshheading:12165507-T-Lymphocytes
pubmed:year
2002
pubmed:articleTitle
Thymocyte apoptosis induced by T cell activation is mediated by glucocorticoids in vivo.
pubmed:affiliation
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't