Plasmacytoid dendritic cells enhance mortality during lethal influenza infections by eliminating virus-specific CD8 T cells.
Previous studies have shown that the reduction in CD8 T cell immunity observed during high-dose influenza A virus (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.
Langlois
Ryan A
RA
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
Legge
Kevin L
KL
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D015536:Down-Regulation / Q000276:immunology; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology
D016827:CD8 Antigens; C431698:CD8alpha antigen; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D019014:fas Receptor