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Beyer, M.* ; Abdullah, Z.* ; Chemnitz, J.M.* ; Maisel, D.* ; Sander, J.* ; Lehmann, C.* ; Thabet, Y.* ; Shinde, P.V.* ; Schmidleithner, L.* ; Köhne, M.* ; Trebicka, J.* ; Schierwagen, R.* ; Hofmann, A.* ; Popov, A.* ; Lang, K.S.* ; Oxenius, A.* ; Buch, T.* ; Kurts, C.* ; Heikenwälder, M. ; Fätkenheuer, G.* ; Lang, P.A.* ; Hartmann, P.* ; Knolle, P.A.* ; Schultze, J.L.*

Tumor-necrosis factor impairs CD4+ T cell-mediated immunological control in chronic viral infection.

Nat. Immunol. 17, 593-603 (2016)
Anhang DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Persistent viral infections are characterized by the simultaneous presence of chronic inflammation and T cell dysfunction. In prototypic models of chronicity-infection with human immunodeficiency virus (HIV) or lymphocytic choriomeningitis virus (LCMV)-we used transcriptome-based modeling to reveal that CD4(+) T cells were co-exposed not only to multiple inhibitory signals but also to tumor-necrosis factor (TNF). Blockade of TNF during chronic infection with LCMV abrogated the inhibitory gene-expression signature in CD4(+) T cells, including reduced expression of the inhibitory receptor PD-1, and reconstituted virus-specific immunity, which led to control of infection. Preventing signaling via the TNF receptor selectively in T cells sufficed to induce these effects. Targeted immunological interventions to disrupt the TNF-mediated link between chronic inflammation and T cell dysfunction might therefore lead to therapies to overcome persistent viral infection.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Lymphocytic Choriomeningitis Virus; Nf-kappa-b; Persistent Lcmv Infection; Factor-alpha; Type-1 Infection; I Interferons; Tnf-alpha; Exhaustion; Differentiation; Activation
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 17, Heft: 5, Seiten: 593-603 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
DOI 10.1038/ni.3399
WOS ID WOS:000374323100019
PubMed ID 26950238
Erfassungsdatum 2016-03-09
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