Abstract
Thymocyte development requires an integration of extracellular cues to enforce lineage commitment at multiple defined checkpoints in a stage-specific manner. Critical signals from the pre-TCR, Notch, and the receptor for interleukin-7 (IL-7) dictate cellular differentiation from the CD4-CD8- (double negative) stage to the CD4+CD8+ (double positive) stage. The PI3K/Akt signaling pathway is required to translate these extracellular signaling events into multiple functional outcomes including cellular survival, proliferation, differentiation, and allelic exclusion at the β-selection checkpoint. However, a complete understanding of the contributions made by the PI3K/Akt pathway in thymocyte development has not been straightforward. This review highlights studies that support the model that the PI3K/Akt pathway is essential for thymocyte survival. We provide new evidence that Akt-mediated survival is not solely due to the increased expression of Bcl-xL but also is a consequence of the role played by Akt to support metabolism in proliferating thymocytes.
Original language | English (US) |
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Pages (from-to) | 104-110 |
Number of pages | 7 |
Journal | Immunology Letters |
Volume | 116 |
Issue number | 2 |
DOIs | |
State | Published - Mar 15 2008 |
Externally published | Yes |
Keywords
- Akt
- Bcl-xL
- Metabolism
- PI3K
- TCR
- Thymocyte
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology