TY - JOUR
T1 - Plasmacytoid dendritic cells enhance mortality during lethal influenza infections by eliminating virus-specific CD8 T cells
AU - Langlois, Ryan A.
AU - Legge, Kevin L.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Previous studies have shown that the reduction in CD8 T cell immunity observed during high-dose influenza Avirus (IAV) infection is mediated via lymph node (LN) dendritic cells (DCs) that express Fas ligand (FasL) and drive FasL-Fas (DC-T)-induced apoptosis. However, the specific DC subset(s) within the LN and the additional factors required for DC-mediated elimination of IAV-specific CD8 T cells remain unknown. In this paper, we demonstrate that plasmacytoid DCs (pDCs), which downregulate FasL during sublethal, but not lethal, IAV infection, accumulate to greater numbers within the LNs of lethal dose-infected mice. Further our findings show that pDCs from lethal, but not sublethal, dose IAV infections drive elimination of Fas+ CD8 T cells and that this elimination occurs only in the absence of TCR recognition of IAV peptide-MHC class I complexes. Together, these results suggest that pDCs play a heretofore unknown deleterious role during lethal dose IAV infections by limiting the CD8 T cell response.
AB - Previous studies have shown that the reduction in CD8 T cell immunity observed during high-dose influenza Avirus (IAV) infection is mediated via lymph node (LN) dendritic cells (DCs) that express Fas ligand (FasL) and drive FasL-Fas (DC-T)-induced apoptosis. However, the specific DC subset(s) within the LN and the additional factors required for DC-mediated elimination of IAV-specific CD8 T cells remain unknown. In this paper, we demonstrate that plasmacytoid DCs (pDCs), which downregulate FasL during sublethal, but not lethal, IAV infection, accumulate to greater numbers within the LNs of lethal dose-infected mice. Further our findings show that pDCs from lethal, but not sublethal, dose IAV infections drive elimination of Fas+ CD8 T cells and that this elimination occurs only in the absence of TCR recognition of IAV peptide-MHC class I complexes. Together, these results suggest that pDCs play a heretofore unknown deleterious role during lethal dose IAV infections by limiting the CD8 T cell response.
UR - http://www.scopus.com/inward/record.url?scp=77952753345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952753345&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0902984
DO - 10.4049/jimmunol.0902984
M3 - Article
C2 - 20220091
AN - SCOPUS:77952753345
SN - 0022-1767
VL - 184
SP - 4440
EP - 4446
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -