A Critical Role for Granzymes in Antigen Cross-Presentation through Regulating Phagocytosis of Killed Tumor Cells
- Hoves, S; Sutton, VR; Haynes, NM; Hawkins, ED; Ruiz, DF; Baschuk, N; Sedelies, KA; Schnurr, M; Stagg, J; Andrews, DM; Villadangos, JA; Trapani, JA;
Publication Year 2011-08-01, Volume 187, Issue #3, Page 1166-1175
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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 CD8 alpha(+) DC but not CD8 alpha(-) 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. The Journal of Immunology, 2011, 187: 1166-1175.
- AMER ASSOC IMMUNOLOGISTS
- APOPTOTIC CELLS; DENDRITIC CELLS; IN-VIVO; CYTOTOXIC LYMPHOCYTES; TARGET-CELLS; CALRETICULIN EXPOSURE; CYTOKINE PRODUCTION; MEDIATED APOPTOSIS; DNA FRAGMENTATION; GENE-EXPRESSION
- Publisher's Version
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Creation Date: 2011-08-01 12:00:00Last Modified: 0001-01-01 12:00:00