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

作     者：Aaron Ochel Marcin Cebula Mathias Riehn Upneet Hillebrand Christoph Lipps Reinhold Schirmbeck Hansjorg Hauser Dagmar Wirth 

作者机构：Model Systems for Infection and Immunity Helmholtz Centre for Infection Research Inhoffenstr. 7 38124 Braunschweig Germany Clinic for Internal Medicine I University Hospital UIm Albert-Einstein-Allee 23 89081 UIm Germany Experimental Hematology Medical School Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Current address Institute for Immunology Justus-Liebig University Giessen BFS Schubertstr. 81 35390 Giessen Germany 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2016年第13卷第6期

页      面：805-815页

核心收录：

学科分类：10[医学] 

基　　金：HZI Grad School Hannover Biomedical Research School (HBRS) Center for Infection Biology (ZIB) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Wi2648] Helmholtz Association cross-program activity 'Metabolic Dysfunction and Human Disease' Helmholtz Initiative for Synthetic Biology 

主　　题：antigen load chronicity immune modulation T-cell exhaustion 

摘      要：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.