title: T Cell Help Amplifies Innate Signals in CD8(+) DCs for Optimal CD8(+) T Cell Priming.
abstract: DCs often require stimulation from CD4(+) T cells to propagate CD8(+) T cell responses, but precisely how T cell help optimizes the priming capacity of DCs and why this appears to differ between varying types of CD8(+) T cell immunity remains unclear. We show that CD8(+) T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4(+) T cells to provide IL-15. This was not an additive effect but resulted from CD4(+) T cells amplifying DC production of IL-15 in response to IFN-α/β. We also observed that increased innate stimulation reversed the helper dependence of CD8(+) T cell priming and that the innate stimulus, rather than the CD4(+) T cells themselves, determined how "help'" was integrated into the priming response by DCs. These findings identify T cell help as a flexible means to amplify varying suboptimal innate signals in DCs.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Marie
authors.initials: M
authors.lastname: Greyer
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Angus T
authors.initials: AT
authors.lastname: Stock
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Davey
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Tebartz
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Annabell
authors.initials: A
authors.lastname: Bachem
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3088, Australia.
authors.forename: Meredith
authors.initials: M
authors.lastname: O'Keeffe
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: sbedoui@unimelb.edu.au.
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016899:Interferon-beta / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D012871:Skin Diseases / Q000473:pathology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D018925:Chemokines; C508034:Ifnar2 protein, mouse; D016898:Interferon-alpha; D019409:Interleukin-15; D015850:Interleukin-6; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta