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Surprisingly, we show, using live cell microscopy and other methodologies, that cells targeted by allogenic CD8+ cytotoxic T lymphocyte (CTL) raised in cathepsin C\u2013null mice die through perforin-dependent apoptosis indistinguishable from that induced by wild-type CTL. The cathepsin C\u2013null CTL expressed reduced but still appreciable granzyme B activity, but minimal granzyme A activity. Also, in contrast to mice with inactivation of both their granzyme A\/B genes, cathepsin C deficiency did not confer susceptibility to ectromelia virus infection in vivo. Overall, our results indicate that although cathepsin C clearly generates the majority of granzyme B activity, some is still generated in its absence, pointing to alternative mechanisms for granzyme B processing and activation. Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A\/B deficiency.<\/jats:p>","DOI":"10.1083\/jcb.200609077","type":"journal-article","created":{"date-parts":[[2007,2,6]],"date-time":"2007-02-06T01:36:15Z","timestamp":1170725775000},"page":"425-433","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Residual active granzyme B in cathepsin C\u2013null lymphocytes is sufficient for perforin-dependent target cell apoptosis"],"prefix":"10.1083","volume":"176","author":[{"given":"Vivien R.","family":"Sutton","sequence":"first","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel J.","family":"Waterhouse","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie A.","family":"Browne","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Sedelies","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Ciccone","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Anthony","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aulikki","family":"Koskinen","sequence":"additional","affiliation":[{"name":"2Viral Immunology, Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Mullbacher","sequence":"additional","affiliation":[{"name":"2Viral Immunology, Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Trapani","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,2,5]]},"reference":[{"key":"2023072908345159900_BIB1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1172\/JCI0213462","volume":"109","year":"2002","journal-title":"J. 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