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Do CTL kill target cells by inducing apoptosis?

P A Henkart1, M S Williams, C M Zacharchuk

  • 1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA.

Seminars in Immunology
|April 1, 1997
PubMed

Insights

Caspase inhibitors block apoptosis induced by Fas ligand but not target cell death from cytotoxic T lymphocyte (CTL) granule exocytosis. These inhibitors prevent apoptosis hallmarks without affecting CTL-mediated target cell lysis.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • ICE-family proteases, known as caspases, are key mediators of apoptotic cell death.
  • T lymphocytes utilize caspases in various apoptotic pathways.
  • Cytotoxic T lymphocytes (CTLs) induce target cell death through distinct mechanisms.

Purpose of the Study:

  • To investigate the efficacy of caspase inhibitors in blocking CTL-induced target cell death.
  • To differentiate the role of caspases in CTL-mediated apoptosis versus lysis.

Main Methods:

  • Utilized caspase inhibitors to block apoptosis.
  • Compared the effects of inhibitors on target cell death induced by Fas ligand-bearing CTLs versus CTL granule exocytosis.
  • Assessed target cell lysis and apoptotic nuclear damage.

Main Results:

  • Caspase inhibitors efficiently blocked apoptotic target cell death induced by the Fas death pathway.
  • Caspase inhibitors did not detectably block target cell lysis mediated by the CTL granule exocytosis pathway.
  • Apoptotic nuclear damage accompanying granule exocytosis-induced lysis was blocked by caspase inhibitors.

Conclusions:

  • Caspase inhibitors prevent the characteristic features of apoptosis.
  • Caspase inhibitors do not inhibit target cell death mediated by the CTL granule exocytosis pathway, indicating a caspase-independent cell death mechanism.
  • Distinct CTL-mediated cell death pathways exhibit differential sensitivity to caspase inhibition.

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