Granzyme B-induced cell death exerted by ex vivo CTL: discriminating requirements for cell death and some of its signs

Cell Death Differ. 2008 Mar;15(3):567-79. doi: 10.1038/sj.cdd.4402289. Epub 2007 Dec 7.


Granzyme B (gzmB) of cytotoxic T lymphocytes (CTL) is essential for recovery from intracellular pathogens, but the molecular basis of its action is still unresolved. Here, we analyzed gzmB-mediated death pathways under physiological conditions using ex vivo virus-immune CTLs that express perf and gzmB, but not gzmA (gzmB(+)CTL). We show that gzmB(+)CTL abrogate target cell proliferation most likely by inducing cell death, independent of caspases and mitochondrial signaling. In addition, the data reveal that gzmB(+)CTL independently induce pro-apoptotic processes either via caspase-3/-7, leading to plasma membrane perturbance and ROS production or via Bid/Bak/Bax, resulting in cytochrome c release and that both pathways elicit loss of DeltaPsi(m). Our data provide evidence for a pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / physiology
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cell Membrane Permeability
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Granzymes / genetics
  • Granzymes / metabolism*
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Knockout
  • Phosphatidylserines / analysis
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes, Cytotoxic / enzymology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Apoptosis Regulatory Proteins
  • Phosphatidylserines
  • Reactive Oxygen Species
  • Cytochromes c
  • Granzymes
  • Gzmb protein, mouse
  • Caspase 3
  • Caspase 7