Influenza virus and poly(I:C) inhibit MHC class I-restricted presentation of cell-associated antigens derived from infected dead cells captured by human dendritic cells

Davor Frleta, Chun I. Yu, Eynav Klechevsky, Anne Laure Flamar, Gerard Zurawski, Jacques Banchereau, A. Karolina Palucka

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

During viral infection, dendritic cells (DCs) capture infected cells and present viral Ags to CD8+ T cells. However, activated DCs might potentially present cell-associated Ags derived from captured dead cells. In this study, we find that human DCs that captured dead cells containing the TLR3 agonist poly(I:C) produced cytokines and underwent maturation, but failed to elicit autologous CD8+ T cell responses against Ags of dead cells. Accordingly, DCs that captured dead cells containing poly(I:C), or influenza virus, are unable to activate CD8+ T cell clones specific to cell-associated Ags of captured dead cells. CD4+ T cells are expanded with DCs that have captured poly(I:C)-containing dead cells, indicating the inhibition is specific for MHC class I-restricted cross-presentation. Furthermore, these DCs can expand naive allogeneic CD8+ T cells. Finally, soluble or targeted Ag is presented when coloaded onto DCs that have captured poly(I:C)-containing dead cells, indicating the inhibition is specific for dead cell cargo that is accompanied by viral or poly(I:C) stimulus. Thus, DCs have a mechanism that prevents MHC class I-restricted cross-presentation of cell-associated Ag when they have captured dead infected cells.

Original languageEnglish
Pages (from-to)2766-2776
Number of pages11
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009

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