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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)
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Lymphocytic Choriomeningitis Virus; Nf-kappa-b; Persistent Lcmv Infection; Factor-alpha; Type-1 Infection; I Interferons; Tnf-alpha; Exhaustion; Differentiation; Activation
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Quellenangaben Volume: 17, Issue: 5, Pages: 593-603 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York
Reviewing status Peer reviewed