Document Detail


Serine Protease Inhibitor 6 Is Required To Protect Dendritic Cells from the Kiss of Death.
MedLine Citation:
PMID:  22227570     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 CD8α DC. The impaired survival of Spi6 knockout CD8α 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.
Authors:
Elena Lovo; Manling Zhang; Lihui Wang; Philip G Ashton-Rickardt
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-6
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  -     ISSN:  1550-6606     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
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