Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis
AuthorWaterhouse, NJ; Sutton, VR; Sedelies, KA; Ciccone, A; Jenkins, M; Turner, SJ; Bird, PI; Trapani, JA
Source TitleJOURNAL OF CELL BIOLOGY
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sWATERHOUSE, NIGEL; Turner, Stephen; Trapani, Joseph; Jenkins, Misty-Rayna
Microbiology and Immunology
Sir Peter MacCallum Department of Oncology
Medical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsWaterhouse, N. J., Sutton, V. R., Sedelies, K. A., Ciccone, A., Jenkins, M., Turner, S. J., Bird, P. I. & Trapani, J. A. (2006). Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis. JOURNAL OF CELL BIOLOGY, 173 (1), pp.133-144. https://doi.org/10.1083/jcb.200510072.
Access StatusOpen Access
Cytotoxic T lymphocyte (CTL)-induced death triggered by the granule exocytosis pathway involves the perforin-dependent delivery of granzymes to the target cell. Gene targeting has shown that perforin is essential for this process; however, CTL deficient in the key granzymes A and B maintain the ability to kill their targets by granule exocytosis. It is not clear how granzyme AB(-/-) CTLs kill their targets, although it has been proposed that this occurs through perforin-induced lysis. We found that purified granzyme B or CTLs from wild-type mice induced classic apoptotic cell death. Perforin-induced lysis was far more rapid and involved the formation of large plasma membrane protrusions. Cell death induced by granzyme AB(-/-) CTLs shared similar kinetics and morphological characteristics to apoptosis but followed a distinct series of molecular events. Therefore, CTLs from granzyme AB(-/-) mice induce target cell death by a unique mechanism that is distinct from both perforin lysis and apoptosis.
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