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

J Immunol. 2009 Mar 1;182(5):2766-76. doi: 10.4049/jimmunol.0801720.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Coculture Techniques
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / virology*
  • Growth Inhibitors / immunology*
  • HLA-A2 Antigen / immunology*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunosuppression Therapy* / methods
  • Influenza A virus / immunology*
  • Lymphocyte Activation / immunology
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / virology*
  • Necrosis
  • Poly I-C / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Cytotoxic / virology

Substances

  • Antigens, Neoplasm
  • Growth Inhibitors
  • HLA-A2 Antigen
  • Poly I-C

Grants and funding