Landscape of Exhausted Virus-Specific CD8 T Cells in Chronic LCMV Infection.

Animals CD8-Positive T-Lymphocytes / virology Lymphocytic choriomeningitis virus / pathogenicity Mice Viral Load
CD8 T cells chronic viral infection phenotypic plasticity singe cell RNA sequencing tissue-specific phenotypes

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 08 2020
Historique:
received: 25 06 2019
revised: 31 01 2020
accepted: 05 08 2020
entrez: 27 8 2020
pubmed: 28 8 2020
medline: 3 6 2021
Statut: ppublish

Résumé

A hallmark of chronic infections is the presence of exhausted CD8 T cells, characterized by a distinct transcriptional program compared with functional effector or memory cells, co-expression of multiple inhibitory receptors, and impaired effector function, mainly driven by recurrent T cell receptor engagement. In the context of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, most studies focused on studying splenic virus-specific CD8 T cells. Here, we provide a detailed characterization of exhausted CD8 T cells isolated from six different tissues during established LCMV infection, using single-cell RNA sequencing. Our data reveal that exhausted cells are heterogeneous, adopt organ-specific transcriptomic profiles, and can be divided into five main functional subpopulations: advanced exhaustion, effector-like, intermediate, proliferating, or memory-like. Adoptive transfer experiments showed that these phenotypes are plastic, suggesting that the tissue microenvironment has a major impact in shaping the phenotype and function of virus-specific CD8 T cells during chronic infection.

Identifiants

DOI: 10.1016/j.celrep.2020.108078 PMID: 32846135
pubmed: 32846135
pii: S2211-1247(20)31063-9
doi: 10.1016/j.celrep.2020.108078
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108078

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Ioana Sandu (I)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland; Institute of Molecular Systems Biology, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Swiss Institute of Bioinformatics, University of Lausanne, Quartier Sorge-Batiment Amphipole, 1015 Lausanne, Switzerland.

Dario Cerletti (D)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland; Institute of Molecular Systems Biology, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Swiss Institute of Bioinformatics, University of Lausanne, Quartier Sorge-Batiment Amphipole, 1015 Lausanne, Switzerland.

Nathalie Oetiker (N)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Mariana Borsa (M)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Franziska Wagen (F)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Ilaria Spadafora (I)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Suzanne P M Welten (SPM)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Ugne Stolz (U)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.

Annette Oxenius (A)

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. Electronic address: aoxenius@micro.biol.ethz.ch.

Manfred Claassen (M)

Institute of Molecular Systems Biology, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Swiss Institute of Bioinformatics, University of Lausanne, Quartier Sorge-Batiment Amphipole, 1015 Lausanne, Switzerland. Electronic address: claassen@imsb.biol.ethz.ch.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Landscape of Exhausted Virus-Specific CD8 T...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Landscape of Exhausted Virus-Specific CD8 T...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Arenaviridae › Arenavirus › Arénavirus de l'Ancien Monde › Virus de la chorioméningite lymphocytaire › Landscape of Exhausted Virus-Specific CD8 T...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Landscape of Exhausted Virus-Specific CD8 T...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Charge virale › Landscape of Exhausted Virus-Specific CD8 T...