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.
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.
Frleta
Davor
D
Baylor-National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Dallas, Texas 75204, USA.
Yu
Chun I
CI
Klechevsky
Eynav
E
Flamar
Anne-Laure
AL
Zurawski
Gerard
G
Banchereau
Jacques
J
Palucka
A Karolina
AK
D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006131:Growth Inhibitors / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000821:virology*; D009336:Necrosis; D011070:Poly I-C / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000821:virology
D000951:Antigens, Neoplasm; D006131:Growth Inhibitors; D015789:HLA-A2 Antigen; D011070:Poly I-C