Nature communications, 2019-04, Vol.10 (1), p.1507-1507, Article 1507
2019
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- Autor(en) / Beteiligte
- Titel
- NKG2A is a NK cell exhaustion checkpoint for HCV persistence
- Ist Teil von
- Nature communications, 2019-04, Vol.10 (1), p.1507-1507, Article 1507
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Exhaustion of cytotoxic effector natural killer (NK) and CD8 T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O mice permissive for persistent HCV infection, that NK and CD8 T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8 T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8 T cell functions to prevent persistent HCV infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-09212-yTitel-ID: cdi_doaj_primary_oai_doaj_org_article_c0986ae00c854fd2a685f6ada664ab91
- Format
- –
- Schlagworte
- Animals, Antibodies, CD8 antigen, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Chronic infection, Cytokines - immunology, Cytotoxicity, Disease Models, Animal, Exhaustion, Hepacivirus - immunology, Hepatitis, Hepatitis C, Hepatitis C, Chronic - immunology, Hepatitis C, Chronic - virology, Hepatocytes, Hepatocytes - virology, Histocompatibility Antigens Class I - immunology, Infections, Infiltration, Interferon, Interferon-gamma - immunology, Killer Cells, Natural - immunology, Lymphocyte Activation - physiology, Lymphocytes, Lymphocytes T, Membrane Proteins - immunology, Mice, Natural killer cells, NK Cell Lectin-Like Receptor Subfamily C - immunology, NKG2 antigen, Persistent infection, Random Allocation, Viruses, γ-Interferon