title: Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism.
abstract: Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional APCs has been the foundation for the development and use of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the nonconventional property of directly killing tumor cells. The current study investigates the regulation of murine DC cytotoxic function by T lymphocytes. We provide evidence that CD4(+) Th-1, but not Th-2, Th-17 cells, or regulatory T cells, are capable of inducing DC cytotoxic function. IFN-γ was identified as the major factor responsible for Th-1-induced DC tumoricidal activity. Tumor cell killing mediated by Th-1-activated killer DCs was dependent on inducible NO synthase expression and NO production. Importantly, Th-1-activated killer DCs were capable of presenting the acquired Ags from the killed tumor cells to T lymphocytes in vitro or in vivo. These observations offer new possibilities for the application of killer DCs in cancer immunotherapy.
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, AZ 85724-5073, USA.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: LaCasse
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Claire B
authors.initials: CB
authors.lastname: Larmonier
authors.forename: Darya
authors.initials: D
authors.lastname: Alizadeh
authors.forename: Neale
authors.initials: N
authors.lastname: Hanke
authors.forename: Jessica
authors.initials: J
authors.lastname: Kartchner
authors.forename: Elaine
authors.initials: E
authors.lastname: Situ
authors.forename: Sara
authors.initials: S
authors.lastname: Centuori
authors.forename: Michael
authors.initials: M
authors.lastname: Har-Noy
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor
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