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Using mice deficient in serine protease inhibitor 6 (Spi6), we show that Spi6 protects DC from the kiss of death by inhibiting granzyme B (GrB) delivered by CTL. Infection of Spi6 knockout mice with lymphocytic choriomeningitis virus revealed impaired survival of CD8\u03b1 DC. The impaired survival of Spi6 knockout CD8\u03b1 DC resulted in impaired priming and expansion of both primary and memory lymphocytic choriomeningitis virus-specific CTL, which could be corrected by GrB deficiency. The rescue in the clonal burst obtained by GrB elimination demonstrated that GrB was the physiological target through which Spi6 protected DC from CTL. We conclude that the negative regulation of DC priming of CD8 T lymphocyte immunity by CTL killing is mitigated by the physiological inhibition of GrB by Spi6.<\/jats:p>","DOI":"10.4049\/jimmunol.1102667","type":"journal-article","created":{"date-parts":[[2012,1,7]],"date-time":"2012-01-07T05:58:42Z","timestamp":1325915922000},"page":"1057-1063","source":"Crossref","is-referenced-by-count":30,"title":["Serine Protease Inhibitor 6 Is Required To Protect Dendritic Cells from the Kiss of Death"],"prefix":"10.1093","volume":"188","author":[{"given":"Elena","family":"Lovo","sequence":"first","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G","family":"Ashton-Rickardt","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"2025032409500736700_r1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.0105-2896.2010.00892.x","article-title":"Serine protease inhibitors and cytotoxic T lymphocytes","volume":"235","author":"Ashton-Rickardt","year":"2010","journal-title":"Immunol. 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