NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic cell vaccination efficacy.
Recent studies have implicated a possible role for NK cells in regulating dendritic cells (DC) in vitro. In the present study, we demonstrate that immature DC are rapidly eliminated by NK cells in vivo via a pathway dependent on the TNF-related apoptosis-inducing ligand (TRAIL). Elimination of NK cells and/or neutralization of TRAIL function during immunization with immature DC loaded with nonself or tumor Ags significantly enhanced T cell responses to these Ags and Ag-specific tumor immunity. These data suggested that NK cell TRAIL might regulate responses to vaccination by controlling the survival of Ag-loaded DC.
Hayakawa
Yoshihiro
Y
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Screpanti
Valentina
V
Yagita
Hideo
H
Grandien
Alf
A
Ljunggren
Hans-Gustaf
HG
Smyth
Mark J
MJ
Chambers
Benedict J
BJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D006084:Graft Rejection / Q000276:immunology; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D019496:Cancer Vaccines; D006131:Growth Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha