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Effector CD4+ T cells generate intermediate caspase activity and cleavage of caspase-8 substrates
Ravi S Misra1, Dawn M Jelley-Gibbs, Jennifer Q Russell
1University of Vermont, Immunobiology Program, College of Medicine, Burlington, VT 05405, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 22, 2005
Summary
Caspase-8 and caspase-3 are partially activated in effector T cells, influencing cell cycling. Th2 effector cells show higher caspase activity than Th1 cells, impacting T cell activation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Caspase-8 activation is crucial for both apoptosis and T cell activation.
- The precise level of caspase activity and substrate cleavage during T cell activation is not well understood.
Purpose of the Study:
- To quantify caspase activity and identify cleaved substrates in effector CD4(+) T cells.
- To compare caspase activity between Th1 and Th2 effector T cells.
- To investigate the role of caspase activity in T cell cycling initiation.
Main Methods:
- Analysis of caspase activity in murine effector CD4(+) T cells.
- Western blot detection of caspase substrates (c-FLIP(L), RIP1, Bid, ICAD).
- Assessment of T cell cycling initiation following caspase blockade.
Main Results:
- Effector T cells exhibited intermediate caspase activity levels compared to unstimulated and apoptotic cells.
- Caspase-8 substrates (c-FLIP(L), RIP1, Bid) were partially cleaved in effector T cells.
- Caspase-3 activity was not detected via ICAD cleavage.
- Th2 effector T cells displayed higher caspase activity than Th1 effector T cells.
- Caspase inhibition significantly reduced T cell cycling initiation.
Conclusions:
- Effector T cells possess a defined level of caspase-8 and caspase-3 activity essential for initiating cell cycling.
- Differential caspase activity between Th1 and Th2 cells may influence their distinct functions.
- These findings elucidate the role of caspases in T cell activation and proliferation.