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Publication : Serine protease inhibitor 6 is required to protect dendritic cells from the kiss of death.

First Author  Lovo E Year  2012
Journal  J Immunol Volume  188
Issue  3 Pages  1057-63
PubMed ID  22227570 Mgi Jnum  J:181216
Mgi Id  MGI:5309081 Doi  10.4049/jimmunol.1102667
Citation  Lovo E, et al. (2012) Serine protease inhibitor 6 is required to protect dendritic cells from the kiss of death. J Immunol 188(3):1057-63
abstractText  How dendritic cells (DC) present Ag to cytotoxic T cells (CTL) without themselves being killed through contact-mediated cytotoxicity (so-called kiss of death) has proved to be controversial. 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 CD8alpha DC. The impaired survival of Spi6 knockout CD8alpha 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.
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