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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Tumor-necrosis factor impairs CD4+ T cell-mediated immunological control in chronic viral infection.
Nat. Immunol. 17, 593-603 (2016)
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
ISSN (print) / ISBN
1529-2908
e-ISSN
1529-2916
Zeitschrift
Nature Immunology
Quellenangaben
Band: 17,
Heft: 5,
Seiten: 593-603
Verlag
Nature Publishing Group
Verlagsort
New York
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)