title: TNF-induced target cell killing by CTL activated through cross-presentation.
abstract: Viruses can escape cytotoxic T cell (CTL) immunity by avoiding presentation of viral components via endogenous MHC class I antigen presentation in infected cells. Cross-priming of viral antigens circumvents such immune escape by allowing noninfected dendritic cells to activate virus-specific CTLs, but they remain ineffective against infected cells in which immune escape is functional. Here, we show that cross-presentation of antigen released from adenovirus-infected hepatocytes by liver sinusoidal endothelial cells stimulated cross-primed effector CTLs to release tumor necrosis factor (TNF), which killed virus-infected hepatocytes through caspase activation. TNF receptor signaling specifically eliminated infected hepatocytes that showed impaired anti-apoptotic defense. Thus, CTL immune surveillance against infection relies on two similarly important but distinct effector functions that are both MHC restricted, requiring either direct antigen recognition on target cells and canonical CTL effector function or cross-presentation and a noncanonical effector function mediated by TNF.
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, 53105 Bonn, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wohlleber
authors.forename: Hamid
authors.initials: H
authors.lastname: Kashkar
authors.forename: Katja
authors.initials: K
authors.lastname: Gärtner
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Frings
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
authors.forename: Silke
authors.initials: S
authors.lastname: Hegenbarth
authors.forename: Carolin
authors.initials: C
authors.lastname: Börner
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Günter
authors.initials: G
authors.lastname: Hämmerling
authors.forename: Bernd
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Karin
authors.initials: K
authors.lastname: Cederbrant
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Manolis
authors.initials: M
authors.lastname: Pasparakis
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Dienes
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Martin
authors.initials: M
authors.lastname: Krönke
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D007111:Immunity, Cellular / Q000502:physiology; D007157:Immunologic Surveillance / Q000502:physiology; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D061025:Costimulatory and Inhibitory T-Cell Receptors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha