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Fas/Fas ligand signaling during gestational T cell development
Journal of Immunology (Baltimore, Md. : 1950)
|April 29, 1998
Summary
Fas-mediated apoptosis is crucial for early thymocyte development. Thymocytes become sensitive to Fas-induced cell death during development but gain resistance upon T-cell receptor signaling.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Thymocyte development involves intricate regulatory mechanisms.
- Fas (Apo-1/CD95) and its ligand (FasL) mediate apoptosis, but their precise role in thymocyte maturation is not fully understood.
Purpose of the Study:
- To investigate the role of Fas/FasL-mediated apoptosis in gestational thymocyte development.
- To determine the developmental stage at which thymocytes become sensitive or resistant to Fas-mediated apoptosis.
Main Methods:
- Analysis of Fas and FasL mRNA and protein expression during mouse gestation.
- Detection of apoptotic thymocytes in wild-type and Fas-deficient mice.
- Fetal thymic organ cultures treated with anti-Fas antibodies.
- Assessment of thymocyte sensitivity to Fas-mediated apoptosis at different developmental stages.
Main Results:
- High FasL expression correlated with early thymocyte apoptosis around gestational day 15.
- Fas-mediated apoptosis sensitivity emerged during the CD4-CD8- to CD4+CD8+ transition.
- Mature thymocytes and those receiving T-cell receptor signals became resistant to Fas-mediated apoptosis.
Conclusions:
- Fas plays a critical role in regulating apoptosis during early thymocyte development.
- T-cell receptor signaling confers resistance to Fas-mediated apoptosis, highlighting a survival mechanism during thymocyte maturation.