Linked Life Data

10229809

Source:http://linkedlifedata.com/resource/pubmed/id/10229809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-6-14
pubmed:abstractText
Thymic selection is controlled in part by the avidity of the interaction between thymocytes and APCs. In agreement, the selective outcome can be modulated by altering the expression levels of selecting ligands on APCs. Here we test the converse proposition, i. e., whether changing TCR levels on thymocytes can alter the selective outcome. To this end, we have generated mice in which all thymocytes express two transgenic TCRs simultaneously (dual TCR-expressing (DTE) mice), the class I-restricted HY TCR and the class II-restricted AND TCR. Due to mutual dilution, surface expression levels of the two individual transgenic TCRs are diminished in DTE relative to single TCR-expressing mice. We find that thymic selection is highly sensitive to these reductions in TCR surface expression. Positive selection mediated by the AND and HY TCRs is severely impaired or abolished, respectively. Negative selection of the HY TCR in male DTE mice is also partly blocked, leading to the appearance of significant numbers of double positive thymocytes. Also, in the periphery of male, but not female, DTE mice, substantial numbers of single positive CD8bright cells accumulate, which are positively selected in the thymus but by a highly inefficient hemopoietic cell-dependent process. Overall our results favor the interpretation that the outcome of thymic selection is not determined solely by avidity and the resulting signal intensity, but is also constrained by other factors such as the nature of the ligand and/or its presentation by different subsets of APCs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5764-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10229809-Animals, pubmed-meshheading:10229809-Antigen-Presenting Cells, pubmed-meshheading:10229809-CD4-Positive T-Lymphocytes, pubmed-meshheading:10229809-CD8-Positive T-Lymphocytes, pubmed-meshheading:10229809-Clonal Deletion, pubmed-meshheading:10229809-Epithelial Cells, pubmed-meshheading:10229809-Female, pubmed-meshheading:10229809-Gene Rearrangement, T-Lymphocyte, pubmed-meshheading:10229809-H-2 Antigens, pubmed-meshheading:10229809-Histocompatibility Antigens Class I, pubmed-meshheading:10229809-Histocompatibility Antigens Class II, pubmed-meshheading:10229809-Homeodomain Proteins, pubmed-meshheading:10229809-Ligands, pubmed-meshheading:10229809-Lymphocyte Activation, pubmed-meshheading:10229809-Male, pubmed-meshheading:10229809-Mice, pubmed-meshheading:10229809-Mice, Transgenic, pubmed-meshheading:10229809-Receptors, Antigen, T-Cell, pubmed-meshheading:10229809-Sex Factors, pubmed-meshheading:10229809-Thymus Gland, pubmed-meshheading:10229809-beta 2-Microglobulin
pubmed:year
1999
pubmed:articleTitle
Limiting TCR expression leads to quantitative but not qualitative changes in thymic selection.
pubmed:affiliation
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't