Presentation of hepatocellular antigens

• Type of Material: Article
• Authors: Arash Grakoui, Emory University; Ian Nicholas Crispe, University of Washington
• Language: English
• Date: 2016-05-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Chinese Society of Immunology and The University of Science and Technology
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1038/cmi.2015.109
• Title of Journal or Parent Work: Cellular and Molecular Immunology
• ISSN: 1672-7681
• Volume: 13
• Issue: 3
• Start Page: 293
• End Page: 300
• Grant/Funding Information: We acknowledge the support provided by the National Institutes of Health (PHS grants R01AI070101 and R21AI118337 to A.G.; and R01AI114630 and R21AI114827 to I.N.C.) and ORIP/OD P51OD011132 (formerly NCRR P51RR000165) to the Yerkes National Primate Research Center.
• Keywords: SINUSOIDAL ENDOTHELIAL-CELLS; liver; DIET-INDUCED OBESITY; LISTERIA-MONOCYTOGENES; INFECTED HEPATOCYTES; HEPATITIS-C VIRUS; tolerance; hepatocytes; CD8(+) T-CELLS; Life Sciences & Biomedicine; HIGH-FAT-DIET; immunity; LIVER-INJURY; Immunology; MYELOID DENDRITIC CELLS; KUPFFER CELLS
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

Abstract

The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liver-stage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology.