Target Cell Lysis by CTL Granule Exocytosis Is Independent of ICE/Ced-3 Family Proteases

Immunity. 1997 Feb;6(2):209-15. doi: 10.1016/s1074-7613(00)80427-6.

Abstract

Activation of ICE/Ced-3 family proteases (caspases) has been proposed to mediate both the granule exocytosis and Fas-Fas ligand pathways of rapid target cell death by cytotoxic T lymphocytes. In agreement with this model, two peptide fluoromethyl ketone caspase inhibitors and baculovirus p35 blocked apoptotic nuclear damage and target cell lysis by the CTL-mediated Fas-Fas ligand pathway. The peptide caspase inhibitors also blocked drug-induced apoptotic cell death in tumor cells. In contrast, the caspase inhibitors blocked CTL granule exocytosis-induced target apoptotic nuclear damage, but did not inhibit target lysis. These results are consistent with recent demonstrations that granzyme B can activate caspases leading to apoptotic nuclear damage, but show that target cell lysis by CTL granule exocytosis occurs by a caspase-independent pathway.

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins
  • Caspase 1
  • Caspases*
  • Cysteine Endopeptidases / analysis*
  • Cytoplasmic Granules / metabolism*
  • Cytotoxicity, Immunologic / immunology*
  • Exocytosis / immunology*
  • Helminth Proteins / analysis*
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / enzymology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans
  • Caspase 1