Serpinb9 (Spi6)-deficient mice are impaired in dendritic cell-mediated antigen cross-presentation
Details
Publication Year 2012-10,Volume 90,Issue #9,Page 841-851
Journal Title
IMMUNOLOGY AND CELL BIOLOGY
Publication Type
Journal Article
Abstract
Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (GrB) that protects activated cytotoxic lymphocytes from apoptosis. We show here that the CD8(+) subset of splenic dendritic cells (DC), specialized in major histocompatibility complex class I (MHC I) presentation of exogenous antigens (cross-presentation), produce high levels of Sb9. Mice deficient in Sb9 are unable to generate a cytotoxic T-cell response against cell-associated antigen by cross-presentation, but maintain normal MHC-II presentation to helper T cells. This impaired cross-priming ability is autonomous to DC and is evident in animals deficient in both Sb9 and GrB, indicating that this role of Sb9 in DC is GrB-independent. In Sb9-deficient mice, CD8(+) DC develop normally, survive as well as wild-type DC after antigenic challenge, and exhibit unimpaired capacity to take up antigen. Although the core processing machinery is unaffected, Sb9-deficient DC appear to process antigen faster. Our results point to a novel, GrB-independent role for Sb9 in DC cross-priming. Immunology and Cell Biology (2012) 90, 841-851; doi:10.1038/icb.2012.29; published online 17 July 2012
Publisher
NATURE PUBLISHING GROUP
Keywords
GRANZYME-B INHIBITOR; CYTOTOXIC T-CELLS; IN-VIVO; THIMET OLIGOPEPTIDASE; CUTTING EDGE; STEADY-STATE; CD8(+); PROTECTS; LYMPHOCYTES; EXPRESSION
Research Division(s)
Immunology
Terms of Use/Rights Notice
© 2013 Australasian Society for Immunology


Creation Date: 2012-10-01 12:00:00
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