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Endocytosis by target cells: an essential means for perforin- and granzyme-mediated killing

Cellular & Molecular Immunology volume 9, pages 5–6 (2012)Cite this article

Despite the critical role of cell-mediated immunity in defense against intracellular pathogens, cancer immunosurveillance and development of autoimmunity, the precise mechanisms governing the killing of target cells by cytotoxic T cells (CTLs) and natural killer (NK) cells have remained poorly defined. In a study published in Nature Immunology, Thiery and colleagues have for the first time visualized the movement of the cytotoxic granule proteins perforin and granzymes from the killer cell to the target cell, challenging the textbook model of granule-mediated cytotoxicity and providing direct evidence for a multistep endocytosis-mediated mechanism for the entry of granzymes to the target cell's cytoplasm.1

Since the first observations of azurophilic granules in CTLs and NK cells and the identification of perforin in the 1980s,2, 3 a one-step model of cell-mediated killing has been widely accepted in spite of several inconsistencies. According to this model, exocytosis of cytoplasmic granules results in the release of perforin, which multimerizes to form large pores in the plasma membrane of the target cell, allowing entry of other granule proteins, including the serine proteases belonging to the granzyme family. Granzymes initiate apoptosis both through cleavage of caspase 3 and Bid and through caspase-independent mechanisms.4

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References

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  1. Department of Immunology, Duke University Medical Center, Durham, NC, USA

    Claire Gordy & You-Wen He

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  1. Claire Gordy
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  2. You-Wen He
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Correspondence to You-Wen He.

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Gordy, C., He, YW. Endocytosis by target cells: an essential means for perforin- and granzyme-mediated killing. Cell Mol Immunol 9, 5–6 (2012). https://doi.org/10.1038/cmi.2011.45

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