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Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.
Ochel, Aaron Cebula, Marcin Riehn, Mathias Hillebrand, Upneet Lipps, Christoph Schirmbeck, Reinhold Hauser, Hansjoerg Wirth, Dagmar
Ochel, Aaron
Cebula, Marcin
Riehn, Mathias
Hillebrand, Upneet
Lipps, Christoph
Schirmbeck, Reinhold
Hauser, Hansjoerg
Wirth, Dagmar
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2016-11
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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.
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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.
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en
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2042-0226