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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6777
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pubmed:dateCreated |
2000-4-21
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pubmed:abstractText |
Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins. These precursors have unique, clonally distributed T-cell receptors with unpredictable specificity for the self-MHC molecules involved in this differentiation process. However, the mature T cells that emerge express only the CD4 (MHC class II-binding) or CD8 (MHC class I-binding) co-receptor that complements the MHC class-specificity of the T-cell receptor. How this matching of co-receptor-defined lineage and T-cell-receptor specificity is achieved remains unknown, as does whether signalling by the T-cell receptors, co-receptors and/or general cell-fate regulators such as Notch-1 contributes to initial lineage choice, to subsequent differentiation processes or to both. Here we show that the CD4 versus CD8 lineage fate of immature thymocytes is controlled by the co-receptor-influenced duration of initial T-cell receptor-dependent signalling. Notch-1 does not appear to be essential for this fate determination, but it is selectively required for CD8+ T-cell maturation after commitment directed by T-cell receptors. This indicates that the signals constraining CD4 versus CD8 lineage decisions are distinct from those that support subsequent differentiation events such as silencing of co-receptor loci.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD69 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Notch1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
404
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
506-10
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10761920-Animals,
pubmed-meshheading:10761920-Antigens, CD,
pubmed-meshheading:10761920-Antigens, CD4,
pubmed-meshheading:10761920-Antigens, CD8,
pubmed-meshheading:10761920-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:10761920-CD4-Positive T-Lymphocytes,
pubmed-meshheading:10761920-CD8-Positive T-Lymphocytes,
pubmed-meshheading:10761920-Cell Lineage,
pubmed-meshheading:10761920-Cells, Cultured,
pubmed-meshheading:10761920-Female,
pubmed-meshheading:10761920-Lectins, C-Type,
pubmed-meshheading:10761920-Leukopoiesis,
pubmed-meshheading:10761920-Ligands,
pubmed-meshheading:10761920-Major Histocompatibility Complex,
pubmed-meshheading:10761920-Male,
pubmed-meshheading:10761920-Membrane Proteins,
pubmed-meshheading:10761920-Mice,
pubmed-meshheading:10761920-Mice, Inbred C57BL,
pubmed-meshheading:10761920-Mice, Transgenic,
pubmed-meshheading:10761920-Models, Immunological,
pubmed-meshheading:10761920-Receptor, Notch1,
pubmed-meshheading:10761920-Receptors, Antigen, T-Cell,
pubmed-meshheading:10761920-Receptors, Cell Surface,
pubmed-meshheading:10761920-Signal Transduction,
pubmed-meshheading:10761920-Thymus Gland,
pubmed-meshheading:10761920-Time Factors,
pubmed-meshheading:10761920-Transcription Factors
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pubmed:year |
2000
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pubmed:articleTitle |
The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate.
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pubmed:affiliation |
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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