Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B

Carlo Ferrari and colleagues reveal that hepatitis B virus (HBV) specific CD8 T cells from individuals with chronic HBV infections have extensive mitochondrial dysfunction that contributes to impaired antiviral activity but can be targeted with antioxidants. Hepatitis B virus (HBV)-specific CD8 T ce...

Full description

Saved in:

Bibliographic Details
Published in:	Nature Medicine Vol. 23; no. 3; pp. 327 - 336
Main Authors:	Fisicaro, Paola, Barili, Valeria, Montanini, Barbara, Acerbi, Greta, Ferracin, Manuela, Guerrieri, Francesca, Salerno, Debora, Boni, Carolina, Massari, Marco, Cavallo, M Cristina, Grossi, Glenda, Giuberti, Tiziana, Lampertico, Pietro, Missale, Gabriele, Levrero, Massimo, Ottonello, Simone, Ferrari, Carlo
Format:	Journal Article Magazine Article
Language:	English
Published:	New York Nature Publishing Group US 01-03-2017 Nature Publishing Group
Subjects:	13/106 13/31 14/34 38/61 38/71 38/90 631/250 631/250/255/2514 Acute Disease Adult Aged Antioxidants - pharmacology Biomedicine Cancer Research Care and treatment CD8 lymphocytes CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Chronic illnesses Cytokines - immunology Down-Regulation Female Genes Genomes Genomics Health aspects Hepatitis Hepatitis B Hepatitis B - immunology Hepatitis B virus Hepatitis B, Chronic - genetics Hepatitis B, Chronic - immunology Hepatitis B, Chronic - metabolism Humans Infections Infectious Diseases Influenza Life Sciences Lymphocytes Male Membrane Potential, Mitochondrial Metabolic Diseases Microbiology and Parasitology Middle Aged Mitochondria - drug effects Mitochondria - metabolism Mitochondrial diseases Molecular Medicine Neurosciences Physiological aspects Polymerase Chain Reaction Reactive Oxygen Species - metabolism Superoxides - metabolism Transcriptome Variance analysis Viral infections Virology Young Adult Rome Italy Italy
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Carlo Ferrari and colleagues reveal that hepatitis B virus (HBV) specific CD8 T cells from individuals with chronic HBV infections have extensive mitochondrial dysfunction that contributes to impaired antiviral activity but can be targeted with antioxidants. Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants. The results indicate that exhausted HBV-specific CD8 T cells are markedly impaired at multiple levels and show substantial downregulation of various cellular processes centered on extensive mitochondrial alterations. A notable improvement of mitochondrial and antiviral CD8 functions was elicited by mitochondrion-targeted antioxidants, which suggests a central role for reactive oxygen species (ROS) in T cell exhaustion. Thus, mitochondria represent promising targets for novel reconstitution therapies to treat chronic hepatitis B infection.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-8956 1546-170X 1744-7933
DOI:	10.1038/nm.4275