Beyer, Marc ORCID: 0000-0001-9704-148X, Abdullah, Zeinab, Chemnitz, Jens M., Maisel, Daniela, Sander, Jil, Lehmann, Clara ORCID: 0000-0002-7042-1578, Thabet, Yasser, Shinde, Prashant V., Schmidleithner, Lisa, Koehne, Maren, Trebicka, Jonel, Schierwagen, Robert ORCID: 0000-0002-2195-3666, Hofmann, Andrea, Popov, Alexey, Lang, Karl S., Oxenius, Annette, Buch, Thorsten ORCID: 0000-0002-2236-9074, Kurts, Christian, Heikenwalder, Mathias, Faetkenheuer, Gerd, Lang, Philipp A., Hartmann, Pia, Knolle, Percy A. ORCID: 0000-0003-2983-0414 and Schultze, Joachim L. (2016). Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection. Nat. Immunol., 17 (5). S. 593 - 608. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1529-2916

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Beyer, MarcUNSPECIFIEDorcid.org/0000-0001-9704-148XUNSPECIFIED
Abdullah, ZeinabUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chemnitz, Jens M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maisel, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, JilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, ClaraUNSPECIFIEDorcid.org/0000-0002-7042-1578UNSPECIFIED
Thabet, YasserUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shinde, Prashant V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidleithner, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehne, MarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trebicka, JonelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schierwagen, RobertUNSPECIFIEDorcid.org/0000-0002-2195-3666UNSPECIFIED
Hofmann, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popov, AlexeyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, Karl S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oxenius, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buch, ThorstenUNSPECIFIEDorcid.org/0000-0002-2236-9074UNSPECIFIED
Kurts, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heikenwalder, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, Philipp A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, PiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knolle, Percy A.UNSPECIFIEDorcid.org/0000-0003-2983-0414UNSPECIFIED
Schultze, Joachim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-277396
DOI: 10.1038/ni.3399
Journal or Publication Title: Nat. Immunol.
Volume: 17
Number: 5
Page Range: S. 593 - 608
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1529-2916
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; NF-KAPPA-B; PERSISTENT LCMV INFECTION; FACTOR-ALPHA; TYPE-1 INFECTION; I INTERFERONS; TNF-ALPHA; EXHAUSTION; DIFFERENTIATION; ACTIVATIONMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27739

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