Abstract
E2A and HEB are basic helix-loop-helix transcription factors essential for T cell development. Complete inhibition of their activities through transgenic overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of thymocytes. Here, we suggest that bHLH proteins play important roles in establishing thresholds for pre-TCR and TCR signaling. Inhibition of their function allows double-negative cells to differentiate without a functional pre-TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find that the transcription factor NF-κB becomes activated in transgenic thymocytes. Further activation of NF-κB exacerbates the loss of thymocytes, whereas inhibition of NF-κB leads to the rescue of double-positive thymocytes. Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR signaling and their removal causes hyperactivation and apoptosis of thymocytes.
Original language | English (US) |
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Pages (from-to) | 9-21 |
Number of pages | 13 |
Journal | Immunity |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases