TY - JOUR
T1 - 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
AU - Frleta, Davor
AU - Yu, Chun I.
AU - Klechevsky, Eynav
AU - Flamar, Anne Laure
AU - Zurawski, Gerard
AU - Banchereau, Jacques
AU - Palucka, A. Karolina
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=64849110817&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0801720
DO - 10.4049/jimmunol.0801720
M3 - Article
C2 - 19234171
AN - SCOPUS:64849110817
SN - 0022-1767
VL - 182
SP - 2766
EP - 2776
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -