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Bax deficiency partially corrects interleukin-7 receptor alpha deficiency
Annette R Khaled1, Wen Qing Li, Jiaqiang Huang
1Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute - Frederick, MD 21702, USA.
Immunity
|November 16, 2002
Summary
Bax protein protects against cell death caused by Interleukin-7 (IL-7) deficiency during early T cell development. However, this protective effect diminishes over time in mice lacking the IL-7 receptor alpha chain (IL-7R).
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Cytokines are crucial for hematopoiesis, partly by preventing apoptosis.
- Interleukin-7 (IL-7) is essential for normal T cell development.
- The pro-apoptotic protein Bax plays a role in cell death pathways.
Purpose of the Study:
- To investigate the role of Bax in T cell development in the absence of IL-7 signaling.
- To determine if Bax mediates cell death due to IL-7 receptor alpha chain (IL-7R) deficiency.
Main Methods:
- Generated mice deficient in both Bax and IL-7R.
- Analyzed thymocyte development and cellularity at different ages (birth, 4 weeks, 12 weeks).
- Assessed the involvement of other BH3-only proteins (Bad, Bim) in the IL-7-mediated death pathway.
Main Results:
- Complete recovery of alphabeta thymocyte development was observed in young Bax/IL-7R-deficient mice (up to 4 weeks).
- By 12 weeks, thymic cellularity in Bax/IL-7R-deficient mice decreased to levels seen in IL-7R-deficient mice.
- The BH3-only proteins Bad and Bim were identified as part of the death pathway repressed by IL-7.
Conclusions:
- Bax is essential for mediating cell death induced by IL-7 deficiency in young mice.
- The protective role of Bax against IL-7 deficiency diminishes with age.
- IL-7 signaling represses a death pathway involving Bax, Bad, and Bim during T cell development.