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

Pardo, J.; Wallich, R.; Martin, P.; Urban, C.; Rongvaux, A.; Flavell, R. A.; Müllbacher, A.; Borner, C.; Simon, M. M.

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

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Pardo, J.
Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Martin, P.
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Simon, M. M.
Max Planck Society;

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Citation

Pardo, J., Wallich, R., Martin, P., Urban, C., Rongvaux, A., Flavell, R. A., et al. (2008). Granzyme B-induced cell death exerted by ex vivo CTL: discriminating requirements for cell death and some of its signs. Cell Death and Differentiation, 15, 567-579.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-9109-D

Abstract

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 ΔΨ_m. Our data provide evidence for a pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors.