Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620663
Title:
Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.
Authors:
Ochel, Aaron; Cebula, Marcin; Riehn, Mathias; Hillebrand, Upneet; Lipps, Christoph; Schirmbeck, Reinhold; Hauser, Hansjörg ( /0000-0002-4418-9859 ) ; Wirth, Dagmar ( 0000-0002-2541-6251 )
Abstract:
Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes. 2016, 13 (6):805-815 Cell. Mol. Immunol.
Journal:
Cellular & molecular immunology
Issue Date:
Nov-2016
URI:
http://hdl.handle.net/10033/620663
DOI:
10.1038/cmi.2015.80
PubMed ID:
26412123
Type:
Article
Language:
en
ISSN:
2042-0226
Appears in Collections:
publications of the research group modell systems for infections and immunity (MSYS)

Full metadata record

DC FieldValue Language
dc.contributor.authorOchel, Aaronen
dc.contributor.authorCebula, Marcinen
dc.contributor.authorRiehn, Mathiasen
dc.contributor.authorHillebrand, Upneeten
dc.contributor.authorLipps, Christophen
dc.contributor.authorSchirmbeck, Reinholden
dc.contributor.authorHauser, Hansjörgen
dc.contributor.authorWirth, Dagmaren
dc.date.accessioned2016-12-13T10:27:04Z-
dc.date.available2016-12-13T10:27:04Z-
dc.date.issued2016-11-
dc.identifier.citationEffective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes. 2016, 13 (6):805-815 Cell. Mol. Immunol.en
dc.identifier.issn2042-0226-
dc.identifier.pmid26412123-
dc.identifier.doi10.1038/cmi.2015.80-
dc.identifier.urihttp://hdl.handle.net/10033/620663-
dc.description.abstractLiver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleEffective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCellular & molecular immunologyen

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