title: Natural Killer Dendritic Cells Enhance Immune Responses Elicited by α -Galactosylceramide-Stimulated Natural Killer T Cells.
abstract: Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited by α -galactosylceramide ( α -GC) in mice. The rapid and strong expression of interferon- γ by NKDCs after α -GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated following α -GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited by α -GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated by α -GC-stimulated NKT cells in vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.
authors.affiliation: Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Seokmann
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005699:Galactosylceramides; D007111:Immunity, Cellular / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide