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Apoptosis: Biology and Mechanisms pp 77–102Cite as

Lymphocyte-Mediated Cytolysis: Dual Apoptotic Mechanisms with Overlapping Cytoplasmic and Nuclear Signalling Pathways

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Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 23))

Abstract

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells together comprise cytotoxic lymphocytes (CL), which are the principal basis for the immune system’s detection and destruction of virus-infected or transformed cells. Although CTL and NK cells recognize foreign antigens and become activated in very different ways, both cell types employ the same two contact-dependent cytolytic mechanisms. In the first, the synergy of two granule-bound factors, a calcium-dependent pore-forming protein, perforin, and a collection of proteases (“granzymes”), results in the entry of effector proteases into the target cell cytoplasm and nucleus. The second mechanism involves trimerization of Fas (CD95/APO-1) molecules on susceptible target cells by binding to Fas ligand (FasL/CD95L) expressed on effector lymphocytes, but has no requirement for calcium. Both cytolytic mechanisms can activate a ubiquitous signalling pathway that involves sequential proteolytic events (the caspase cascade) that lead to apoptosis, with the cleavage of structural and enzymatic targets in both the cytoplasm and nucleus.

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Authors and Affiliations

  1. Cellular Cytotoxicity Laboratory, The Austin Research Institute, Studley Road, Heidelberg, 3084, Australia

    Joseph A. Trapani

  2. Nuclear Signalling Laboratory, The John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra City, 2601, Australia

    David A. Jans

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  1. Joseph A. Trapani
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  1. Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Rundle Mall, P.O. Box 14, 5000, Adelaide, SA, Australia

    Sharad Kumar

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Trapani, J.A., Jans, D.A. (1999). Lymphocyte-Mediated Cytolysis: Dual Apoptotic Mechanisms with Overlapping Cytoplasmic and Nuclear Signalling Pathways. In: Kumar, S. (eds) Apoptosis: Biology and Mechanisms. Results and Problems in Cell Differentiation, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69184-6_5

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  • DOI: https://doi.org/10.1007/978-3-540-69184-6_5

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