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CD99 signals caspase-independent T cell death
R D Pettersen1, G Bernard, M K Olafsen
1Department of Pediatric Research and Pediatrics, National Hospital, Oslo, Norway. rolf.pettersen@klinmed.uio.no
Journal of Immunology (Baltimore, Md. : 1950)
|April 6, 2001
Summary
Researchers discovered that engaging specific CD99 epitopes rapidly triggers T cell death via a new caspase-independent pathway. This CD99-mediated T cell death is faster and more potent than Fas or TRAIL signaling, suggesting a novel mechanism for controlling early T cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Fas and TNF receptors are crucial for controlling mature T cells.
- The mechanisms for immune system control of T cells lacking Fas/TNF susceptibility are unknown.
Purpose of the Study:
- To investigate novel death receptors for T cell control.
- To characterize the T cell death pathway induced by CD99.
Main Methods:
- Utilized a new monoclonal antibody (mAb), Ad20, targeting specific CD99 epitopes.
- Assessed T cell death using morphological changes, phosphatidylserine exposure, and propidium iodide uptake.
- Compared CD99-mediated death with Fas and TNF-related apoptosis-inducing ligand (TRAIL) signaling.
Main Results:
- Engagement of CD99 epitopes rapidly induced programmed T cell death in transformed T cell lines.
- CD99-mediated death was faster and more profound than anti-Fas and TRAIL.
- This pathway was independent of CD3, CD4, CD45, p56(lck), and CD47 signaling.
- Normal peripheral T cells did not exhibit Ad20-induced death.
Conclusions:
- CD99 ligation activates a novel, caspase-independent T cell death pathway.
- This pathway is distinct from Fas, TRAIL, and CD47-mediated death.
- CD99 may play a role in the immune control of early T cells.