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TNF dependent induction of inhibitory pathways in CD4+ T cells in HIV and LCMV [HIV-infected individuals]

ABSTRACT: Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17606 | GEO | 2016/03/07

SECONDARY ACCESSION(S): PRJNA118561

REPOSITORIES: GEO

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TNF dependent induction of inhibitory pathways in CD4+ T cells in HIV and LCMV [CD4+ T activation]

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