Linked Life Data

11698441

Source:http://linkedlifedata.com/resource/pubmed/id/11698441

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-11-7
pubmed:abstractText
The pre-TCR complex (TCRbeta-pre-TCRalpha chain (pTalpha)), first expressed in a fraction of CD8(-)4(-)CD44(-)25(+) (DN3) cells, is believed to facilitate or enable an efficient transition from the CD8(-)4(-) double-negative (DN) to the CD8(+)4(+) double-positive (DP) developmental stage. Subsequent to pre-TCR expression, DN3 thymocytes receive survival, proliferation, and differentiation signals, although it is still unclear which of these outcomes are directly induced by the pre-TCR. To address this issue, we generated mice bearing a range of pTalpha transgene copy number under the transcriptional control of the p56(lck) proximal promoter. All lines exhibited increased DN3 cycling, accelerated DN3/4 transition, and improved DN4 survival. However, the high copy number lines also showed a selective reduction in thymic cellularity due to increased apoptosis of DP thymocytes, which could be reversed by the ectopic expression of Bcl-2. Our results suggest that transgenic pTalpha likely caused apoptosis of DP thymocytes due to competitive decrease in surface TCRalphabeta formation. These results highlight the critical importance of precise temporal and stoichiometric regulation of pre-TCR and TCR component expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5689-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Dysregulated expression of pre-Talpha reveals the opposite effects of pre-TCR at successive stages of T cell development.
pubmed:affiliation
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't