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A role for perforin in activation-induced cell death
1Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, Canada. spanerd@srcl.sunnybrook.utoronto.ca
Journal of Immunology (Baltimore, Md. : 1950)
|March 24, 1998
Summary
Perforin, crucial for T cell killing, is essential for T cell death after TCR stimulation. Its absence protects T cells, particularly CD8+ cells, from this Fas-independent apoptosis.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- T cell cytotoxicity is mediated by the granule exocytosis pathway.
- Perforin is a key component of this pathway, forming pores in target cell membranes.
Purpose of the Study:
- To investigate the role of perforin in T cell apoptosis independent of its cytotoxic function.
- To elucidate the mechanism of activation-induced T cell death (AICD) in the absence of perforin.
Main Methods:
- Utilized gene-ablated mice lacking the perforin gene.
- Activated naive T cells were stimulated in vitro via T cell receptor (TCR) complex reaggregation.
- Assessed apoptosis using Fas-independent pathways and monitored perforin expression.
Main Results:
- Perforin-deficient T cells exhibited defective apoptosis following TCR stimulation.
- CD8+ T cells showed the most significant protection from death in the absence of perforin.
- Perforin expression correlated with apoptosis timing; its blockade increased T cell viability.
- Perforin's role was not linked to perforin-dependent fratricidal killing.
Conclusions:
- Perforin plays an intrinsic role in activation-induced T cell death (AICD).
- This perforin-mediated AICD pathway is distinct from Fas- and TNF receptor superfamily-mediated death.
- Perforin may act intracellularly to induce a specific form of T cell death.