Type I IFNs control antigen retention and survival of CD8α + dendritic cells after uptake of tumor apoptotic cells leading to cross-priming

Silvia Lorenzi, Fabrizio Mattei, Antonella Sistigu, Laura Bracci, Francesca Spadaro, Massimo Sanchez, Massimo Spada, Filippo Belardelli, Lucia Gabriele, Giovanna Schiavoni

Research output: Contribution to journalArticle

Abstract

Cross-presentation is a crucial mechanism for generating CD8 T cell responses against exogenous Ags, such as dead cell-derived Ag, and is mainly fulfilled by CD8α+ dendritic cells (DC). Apoptotic cell death occurring in steady-state conditions is largely tolerogenic, thus hampering the onset of effector CD8 T cell responses. Type I IFNs (IFN-I) have been shown to promote cross-priming of CD8 T cells against soluble or viral Ags, partly through stimulation of DC. By using UV-irradiated OVA-expressing mouse EG7 thymoma cells, we show that IFN-I promote intracellular Ag persistence in CD8α+ DC that have engulfed apoptotic EG7 cells, regulating intracellular pH, thus enhancing cross-presentation of apoptotic EG7-derived OVA Ag by CD8α+ DC. Notably, IFN-I also sustain the survival of Ag-bearing CD8α+ DC by selective upmodulation of antiapoptotic genes and stimulate the activation of cross-presenting DC. The ensemble of these effects results in the induction of CD8 T cell effector response in vitro and in vivo. Overall, our data indicate that IFN-I cross-prime CD8 T cells against apoptotic cell-derived Ag both by licensing DC and by enhancing cross-presentation.

Original languageEnglish
Pages (from-to)5142-5150
Number of pages9
JournalJournal of Immunology
Volume186
Issue number9
DOIs
Publication statusPublished - May 1 2011

ASJC Scopus subject areas

  • Immunology

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    Lorenzi, S., Mattei, F., Sistigu, A., Bracci, L., Spadaro, F., Sanchez, M., Spada, M., Belardelli, F., Gabriele, L., & Schiavoni, G. (2011). Type I IFNs control antigen retention and survival of CD8α + dendritic cells after uptake of tumor apoptotic cells leading to cross-priming. Journal of Immunology, 186(9), 5142-5150. https://doi.org/10.4049/jimmunol.1004163