Serpinb9 (Spi6)-deficient mice are impaired in dendritic cell-mediated antigen cross-presentation.
Immunol Cell Biol
; 90(9): 841-51, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22801574
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Serina Endopeptidasas
/
Serpinas
/
Presentación de Antígeno
/
Reactividad Cruzada
/
Proteínas de la Membrana
Idioma:
En
Revista:
Immunol Cell Biol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Australia