title: IFN-producing killer dendritic cells are antigen-presenting cells endowed with T-cell cross-priming capacity.
abstract: IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-gamma, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II(+) IKDC but not NK cross-present MHC class I-restricted antigens derived from MCMV-infected targets to CD8(+) T cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen-presenting cell directly linking innate and adaptive immunity.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Pletneva
authors.forename: Hongni
authors.initials: H
authors.lastname: Fan
authors.forename: Jang-June
authors.initials: JJ
authors.lastname: Park
authors.forename: Vedran
authors.initials: V
authors.lastname: Radojcic
authors.forename: Chunfa
authors.initials: C
authors.lastname: Jie
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Yu
authors.forename: Camie
authors.initials: C
authors.lastname: Chan
authors.forename: Alec
authors.initials: A
authors.lastname: Redwood
authors.forename: Drew
authors.initials: D
authors.lastname: Pardoll
authors.forename: Franck
authors.initials: F
authors.lastname: Housseau
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D007372:Interferons / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018664:Interleukin-12; D007372:Interferons
references.citation: Blood. 2005 Mar 15;105(6):2428-35
references.pmid: 15536145
references.citation: J Infect Dis. 2003 Mar 15;187(6):988-99
references.pmid: 12660946
references.citation: Curr Opin Immunol. 2004 Feb;16(1):96-102
references.pmid: 14734116
references.citation: Immunity. 1997 Jun;6(6):715-26
references.pmid: 9208844
references.citation: J Exp Med. 2007 Oct 29;204(11):2579-90
references.pmid: 17923506
references.citation: Immunity. 2007 Jan;26(1):11-6
references.pmid: 17241957
references.citation: Nat Med. 2006 Feb;12(2):214-9
references.pmid: 16444265
references.citation: J Immunol. 2005 Aug 15;175(4):2071-81
references.pmid: 16081773
references.citation: J Clin Invest. 2004 Dec;114(11):1612-23
references.pmid: 15578093
references.citation: J Immunol. 1987 Aug 15;139(4):1142-7
references.pmid: 3497196
references.citation: Blood. 2007 Jul 1;110(1):186-92
references.pmid: 17392506
references.citation: Nat Med. 2007 Jan;13(1):54-61
references.pmid: 17187072
references.citation: Immunol Rev. 1999 Dec;172:21-8
references.pmid: 10631934
references.citation: Nat Med. 2006 Feb;12(2):207-13
references.pmid: 16444266
references.citation: J Exp Med. 2007 Jun 11;204(6):1441-51
references.pmid: 17535975
references.citation: J Exp Med. 2007 Oct 29;204(11):2561-8
references.pmid: 17923504
references.citation: Blood. 2007 Oct 15;110(8):2965-73
references.pmid: 17562875
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Science. 2007 Jan 5;315(5808):107-11
references.pmid: 17204652
references.citation: Annu Rev Immunol. 1991;9:271-96
references.pmid: 1910679
references.citation: Science. 2003 Feb 28;299(5611):1400-3
references.pmid: 12610307
references.citation: Curr Opin Immunol. 2008 Feb;20(1):89-95
references.pmid: 18249105
references.citation: J Immunol. 2001 Sep 1;167(5):2538-46
references.pmid: 11509593
references.citation: J Immunol. 2004 Sep 15;173(6):3716-24
references.pmid: 15356117
references.citation: J Immunol. 2005 Mar 1;174(5):2612-8
references.pmid: 15728467
references.citation: Blood. 2007 Jun 1;109(11):4825-931
references.pmid: 17317852
references.citation: J Immunol. 2007 Apr 1;178(7):4411-6
references.pmid: 17371998
references.citation: Annu Rev Immunol. 2005;23:975-1028
references.pmid: 15771591
references.citation: Cell Death Differ. 2008 Jan;15(1):58-69
references.pmid: 17948029
references.citation: J Virol. 2003 Jul;77(13):7182-92
references.pmid: 12805417
references.citation: J Immunol. 2008 Feb 1;180(3):1462-70
references.pmid: 18209041
references.citation: Biol Reprod. 2003 Jun;68(6):2024-32
references.pmid: 12606395
references.citation: Immunity. 2007 Sep;27(3):481-92
references.pmid: 17869134
references.citation: Cell. 2006 Jul 14;126(1):205-18
references.pmid: 16839887
references.citation: Blood. 2005 Oct 1;106(7):2252-8
references.pmid: 15933055
references.citation: J Exp Med. 2007 Oct 29;204(11):2569-78
references.pmid: 17923507
references.citation: J Immunol. 1991 Aug 1;147(3):781-7
references.pmid: 1861074