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Regulation of T cell fate by Notch
1Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. erobey@uclink4.berkeley.edu
Annual Review of Immunology
|June 8, 1999
Summary
Notch signaling directs T cell development in the thymus. Activating Notch signaling forces developing T cells into the CD8 lineage, suggesting Notch regulates CD4 vs. CD8 cell fate decisions.
Area of Science:
- Immunology
- Developmental Biology
- Cell Signaling
Background:
- The Notch receptor pathway is crucial for cell fate decisions during embryonic development.
- Notch receptors and ligands are present in the mammalian thymus, suggesting a role in T cell development.
- T cell lineage commitment (CD4 or CD8) is a critical developmental decision in the thymus.
Purpose of the Study:
- To investigate the role of Notch signaling in determining CD4 versus CD8 T cell lineage commitment.
- To explore the potential regulation of Notch signaling by MHC recognition during T cell development.
Main Methods:
- Utilizing a constitutively activated form of Notch in developing thymocytes.
- Analyzing the effects of Notch activation on T cell lineage determination.
- Discussing models for Notch regulation by MHC recognition.
Main Results:
- Forcing Notch activation in developing thymocytes caused a switch from the CD4 to the CD8 lineage.
- This indicates that Notch signaling normally promotes the CD8 lineage fate.
- MHC recognition during positive selection also influences CD4/CD8 choice, suggesting interplay with Notch.
Conclusions:
- Notch signaling plays a significant role in directing CD4+CD8+ thymocyte precursors towards the CD8 lineage.
- MHC recognition may modulate Notch signaling to regulate the CD4/CD8 lineage decision.
- Further models are proposed for how MHC recognition influences Notch-mediated T cell fate determination.