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A Critical Role for Granzymes in Antigen Cross-Presentation through Regulating Phagocytosis of Killed Tumor Cells.
- Source :
-
Journal of Immunology . 8/1/2011, Vol. 187 Issue 3, p1166-1175. 10p. - Publication Year :
- 2011
-
Abstract
- Granzymes A and B (GrAB) are known principally for their role in mediating perforin-dependent death of virus-infected or malignant cells targeted by CTL. In this study, we show that granzymes also play a critical role as inducers of Ag cross-presentation by dendritic cells (DC). This was demonstrated by the markedly reduced priming of naive CD8+ T cells specific for the model Ag OVA both in vitro and in vivo in response to tumor cells killed in the absence of granzymes. Reduced cross-priming was due to impairment of phagocytosis of tumor cell corpses by CD8α+ DC but not CD8α- DC, demonstrating the importance of granzymes in inducing the exposure of prophagocytic "eat-me" signals on the dying target cell. Our data reveal a critical and previously unsuspected role for granzymes A and B in dictating immunogenicity by influencing the mode of tumor cell death and indicate that granzymes contribute to the efficient generation of immune effector pathways in addition to their well-known role in apoptosis induction. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*DENDRITIC cells
*PHAGOCYTOSIS
*IMMUNOLOGY
TUMOR genetics
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 187
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 66170255
- Full Text :
- https://doi.org/10.4049/jimmunol.1001670