| A Critical Role for Granzymes in Antigen Cross-Presentation through Regulating Phagocytosis of Killed Tumor Cells. | |
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MedLine Citation:
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PMID: 21709155 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sabine Hoves; Vivien R Sutton; Nicole M Haynes; Edwin D Hawkins; Daniel Fernández Ruiz; Nikola Baschuk; Karin A Sedelies; Maximilian Schnurr; John Stagg; Daniel M Andrews; Jose A Villadangos; Joseph A Trapani |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-27 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Victoria, Australia; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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