Journal Article

DZNE-2020-04829

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection.

Beyer, M. (First author)DZNE* ; 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. ; Heikenwalder, M. ; Fätkenheuer, G. ; Lang, P. A. ; Hartmann, P. ; Knolle, P. A. ; Schultze, J. L. (Last author)DZNE*

2016
Nature America Inc. New York, NY

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Please use a persistent id in citations: doi:10.1038/ni.3399

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.

Keyword(s): Adolescent (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Animals (MeSH) ; CD4-Positive T-Lymphocytes: immunology (MeSH) ; CD4-Positive T-Lymphocytes: metabolism (MeSH) ; CD4-Positive T-Lymphocytes: virology (MeSH) ; Flow Cytometry (MeSH) ; HEK293 Cells (MeSH) ; HIV: immunology (MeSH) ; HIV: physiology (MeSH) ; HIV Infections: genetics (MeSH) ; HIV Infections: immunology (MeSH) ; HIV Infections: virology (MeSH) ; Host-Pathogen Interactions: immunology (MeSH) ; Humans (MeSH) ; Immunoblotting (MeSH) ; Lymphocytic Choriomeningitis: genetics (MeSH) ; Lymphocytic Choriomeningitis: immunology (MeSH) ; Lymphocytic Choriomeningitis: virology (MeSH) ; Lymphocytic choriomeningitis virus: immunology (MeSH) ; Lymphocytic choriomeningitis virus: physiology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Mice, Transgenic (MeSH) ; Middle Aged (MeSH) ; Oligonucleotide Array Sequence Analysis (MeSH) ; Programmed Cell Death 1 Receptor: genetics (MeSH) ; Programmed Cell Death 1 Receptor: immunology (MeSH) ; Programmed Cell Death 1 Receptor: metabolism (MeSH) ; Receptors, Tumor Necrosis Factor: genetics (MeSH) ; Receptors, Tumor Necrosis Factor: immunology (MeSH) ; Receptors, Tumor Necrosis Factor: metabolism (MeSH) ; Reverse Transcriptase Polymerase Chain Reaction (MeSH) ; Transcriptome: drug effects (MeSH) ; Transcriptome: genetics (MeSH) ; Transcriptome: immunology (MeSH) ; Tumor Necrosis Factor-alpha: immunology (MeSH) ; Tumor Necrosis Factor-alpha: metabolism (MeSH) ; Tumor Necrosis Factor-alpha: pharmacology (MeSH) ; Young Adult (MeSH) ; Programmed Cell Death 1 Receptor ; Receptors, Tumor Necrosis Factor ; Tumor Necrosis Factor-alpha

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Contributing Institute(s):

1. Molecular Immunology in Neurodegeneration (AG Beyer)
2. United epigenomic platform (Schultze - PRECISE)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Beyer, M. (First author)DZNE* ; Abdullah, Z. ; Chemnitz, J. M. ; Maisel, D. ; Sander, J. ; Lehmann, C. ; Thabet, Y. ; Shinde, P. V. ; Schmidleithner, L.Extern* ; Köhne, M. C.Extern* ; Trebicka, J. ; Schierwagen, R. ; Hofmann, A.Extern* ; Popov, A. ; Lang, K. S. ; Oxenius, A. ; Buch, T. ; Kurts, C. ; Heikenwalder, M. ; Fätkenheuer, G. ; Lang, P. A. ; Hartmann, P.Extern* ; Knolle, P. A. ; Schultze, J. L. (Last author)DZNE*
Publisher Correction: Tumor-necrosis factor impairs CD4+ T cell–mediated immunological control in chronic viral infection
Nature immunology 21(9), 1135 (2020) [10.1038/s41590-020-0749-7]2020   Files BibTeX | EndNote: XML, Text | RIS

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