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The Journal of Immunology, 2004, 172: 123-129.
Copyright © 2004 by The American Association of Immunologists

NK Cell TRAIL Eliminates Immature Dendritic Cells In Vivo and Limits Dendritic Cell Vaccination Efficacy 1

Yoshihiro Hayakawa*, Valentina Screpanti{dagger}, Hideo Yagita{ddagger}, Alf Grandien{dagger}, Hans-Gustaf Ljunggren{dagger}, Mark J. Smyth* and Benedict J. Chambers2,{dagger},§

* Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; {dagger} Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; {ddagger} Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and § Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden

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.




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