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Title: Influenza A infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7- and type I IFN-dependent fashion.
Austin Authors: Wei, Joe;Waithman, Jason;Lata, Roleen;Mifsud, Nicole A;Cebon, Jonathan S ;Kay, Thomas;Smyth, Mark J;Sadler, Anthony J;Chen, Weisan
Affiliation: Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Melbourne, Victoria, Australia
Issue Date: 18-Oct-2010
Publication information: Journal of Immunology (baltimore, Md. : 1950) 2010; 185(10): 6013-22
Abstract: The initiation of antitumor immunity relies on dendritic cells (DCs) to cross-present cell-associated tumor Ag to CD8(+) T cells (T(CD8+)) due to a lack of costimulatory molecules on tumor cells. Innate danger signals have been demonstrated to enhance cross-priming of T(CD8+) to soluble as well as virally encoded Ags; however, their effect on enhancing T(CD8+) cross-priming to cell genome-encoded Ags remains unknown. Furthermore, influenza A virus (IAV) has not been shown to enhance antitumor immunity. Using influenza-infected allogeneic cell lines, we show in this study that T(CD8+) responses to cell-associated Ags can be dramatically enhanced due to enhanced T(CD8+) expansion. This enhanced cross-priming in part involves TLR7- but not TLR3-mediated sensing of IAV and is entirely dependent on MyD88 and IFN signaling pathways. We also showed that the inflammasome-induced IL-1 and IFN-γ did not play a role in enhancing cross-priming in our system. We further demonstrated in our ex vivo system that CD8(+) DCs are the only APCs able to prime TCR-transgenic T(CD8+). Importantly, plasmacytoid DCs and CD8(-) DCs were both able to enhance such priming when provided in coculture. These observations suggest that IAV infection of tumor cells may facilitate improved cross-presentation of tumor Ags and may be used to augment clinical vaccine efficacy.
Gov't Doc #: 20956347
DOI: 10.4049/jimmunol.1002129
Type: Journal Article
Subjects: Animals
Antigen Presentation.immunology
Antigens, Neoplasm.immunology
CD8-Positive T-Lymphocytes.immunology
Cancer Vaccines.immunology
Dendritic Cells.immunology
Enzyme-Linked Immunosorbent Assay
Influenza A virus.immunology
Interferon Type I.immunology
Lymphocyte Activation.immunology
Membrane Glycoproteins.immunology
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections.immunology
Polymerase Chain Reaction
Signal Transduction.immunology
Toll-Like Receptor 7.immunology
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