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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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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
Institute(s) Institute of Virology (VIRO)