Correlating Notch Signaling with Thymocyte Maturation

The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of murine Notch-1 as capable of rendering thymomas...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1998-12, Vol.9 (6), p.777-786
Main Authors: Deftos, Michael L, He, You-Wen, Ojala, Ethan W, Bevan, Michael J
Format: Article
Language:English
Subjects:
Animals
Binding Sites
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - drug effects
CD8-Positive T-Lymphocytes - metabolism
Drosophila Proteins
Drug Resistance
Glucocorticoids - pharmacology
Insect Proteins - genetics
Intracellular Fluid
Leukopoiesis
Membrane Proteins - metabolism
Mice
Peptide Mapping
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Receptor, Notch1
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Receptors, Cell Surface - metabolism
Signal Transduction
Thymus Gland
Transcription Factors
Tumor Cells, Cultured
Up-Regulation
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Summary:The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of murine Notch-1 as capable of rendering thymomas resistant to glucocorticoid-induced apoptosis. This effect was confirmed in other T cell lines and in CD4+CD8+ DP thymocytes. Activation of the Notch signaling pathway also upregulated a number of other markers that, like steroid resistance, correlate with DP maturation into both the CD4 and CD8 lineages. These results suggest that Notch signaling is critically involved in the maturation of DP thymocytes into both CD4+ and CD8+ SP thymocytes.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80643-3