Granzyme B; the chalk-mark of a cytotoxic lymphocyte
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BioMed Central
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Commentary
Granzyme B; the chalk-mark of a cytotoxic lymphocyte Nigel J Waterhouse*, Karin A Sedelies and Chris JP Clarke Address: Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, 8006, Australia Email: Nigel J Waterhouse* - [email protected]; Karin A Sedelies - [email protected]; Chris JP Clarke - [email protected] * Corresponding author
Published: 25 October 2004 Journal of Translational Medicine 2004, 2:36
doi:10.1186/1479-5876-2-36
Received: 27 September 2004 Accepted: 25 October 2004
This article is available from: http://www.translational-medicine.com/content/2/1/36 © 2004 Waterhouse et al; licensee BioMed Central Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract During cytotoxic lymphocyte (CL) mediated killing of target cells, granzyme B is released from the CL into the immune synapse. Recent studies have found that ELISPOT-detection of granzyme B correlated well with conventional assays for CL mediated killing. In this way, the released granzyme B can be used to mark the spot where a target cell was murdered. We discuss the benefits and potential limitations of using this assay to measure CL mediated killing of target cells.
Introduction Cytotoxic Lymphocytes (CLs) eliminate virally infected cells or tumour cells either by activating death receptors or by delivering cytotoxic granule proteins (granule exocytosis) to the target cell [1,2]. The ability of a virus or a tumour cell to evade detection or survive an attack by CLs is likely to result in a more aggressive disease. The ability to measure specific killing of target cells by CLs is therefore of great interest to clinicians and researchers alike. Any assay for CL-induced death involves mixed cultures of target and effector cells and must include some means of distinguishing between the two. The current approach is to measure the release of a label, such as 51Cr or, more recently calcein-AM [3], that has been preloaded into the target cells. Radioactivity limits the utility of 51Cr and, although this type of assay is presumed to measure rupture of the plasma membrane (cell lysis), it is not formally known what is being measured.
Discussion Various alternative assays have been developed to assay CL-induced killing of target cells [4-10], however 51Cr remains the gold standard. Recently, Shafer-Weaver et al and others have utilized an interesting strategy aimed at
measuring the functions of effector cells rather than death of the target cell [9,11]. During granule-mediated killing, granule enzymes (granzymes) are transferred to the target cell [2,12]. In the target cell granzyme B, can initiate target cell death by apoptosis [13,14]. Shafer-Weaver et al., [11] demonstrated that detection of granzyme B by
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