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Wohlleber, D.* ; Kashkar, H.* ; Gärtner, K.* ; Frings, M.K.* ; Odenthal, M.* ; Hegenbarth, S.* ; Borner, C.* ; Arnold, B.* ; Hämmerling, G.* ; Nieswandt, B.* ; van Rooijen, N.* ; Limmer, A.* ; Cederbrant, K.* ; Heikenwälder, M. ; Pasparakis, M.* ; Protzer, U. ; Dienes, H.-P.* ; Kurts, C.* ; Krönke, M.* ; Knolle, P.A.*

TNF-induced target cell killing by CTL activated through cross-presentation.

Cell Rep. 2, 478-487 (2012)
Verlagsversion Volltext DOI PMC
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Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter HEPATITIS-B-VIRUS; CD8(+) T-CELLS; ENDOTHELIAL-CELLS; EXOGENOUS ANTIGEN; DENDRITIC CELLS; IMMUNE-RESPONSE; LIVER-DAMAGE; MOUSE MODEL; INFECTIONS; TOLERANCE
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 2, Heft: 3, Seiten: 478-487 Artikelnummer: , Supplement: ,
Verlag Cell Press
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
G-502700-003
G-502700-004
PubMed ID 22939982
Erfassungsdatum 2012-11-15