Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance

Background & Aims In the liver, antigen-presenting cell populations such as Kupffer cells, liver dendritic cells, and liver sinusoidal endothelial cells (LSECs) participate through cross-presentation to CD8 T cells (CTLs) in hepatic immune-regulation and immune-surveillance. The participation of...

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Published in:	Journal of hepatology Vol. 61; no. 3; pp. 600 - 608
Main Authors:	Schölzel, Katrin, Schildberg, Frank A, Welz, Meike, Börner, Carolin, Geiger, Sergej, Kurts, Christian, Heikenwälder, Mathias, Knolle, Percy A, Wohlleber, Dirk
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-09-2014
Subjects:	Animals Cell Proliferation Cells, Cultured Cross-presentation Gastroenterology and Hepatology Gene Expression Regulation - genetics Gene Transfer Techniques Genes, MHC Class I - genetics Hepatic Stellate Cells - immunology Hepatic Stellate Cells - pathology HSC Immunologic Surveillance - genetics Liver - immunology Liver - pathology LSEC Lymphocyte Activation MHC-I Mice Mice, Transgenic Models, Animal Cross-presentation liver sinusoidal endothelial cell HSC hepatic stellate cell MHC-I LSEC
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Summary:	Background & Aims In the liver, antigen-presenting cell populations such as Kupffer cells, liver dendritic cells, and liver sinusoidal endothelial cells (LSECs) participate through cross-presentation to CD8 T cells (CTLs) in hepatic immune-regulation and immune-surveillance. The participation of hepatic stellate cells (HSCs) in immune regulation is controversial. Here we studied HSC’s contribution to antiviral CTL immunity. Methods Flow cytometric analysis of MHC-I molecules at the cell surface of liver cells from mice with cell-type restricted MHC-I expression. Mice with HSC-restricted MHC-I expression were infected with a hepatotropic virus and analyzed for development of viral hepatitis after CTL transfer. Results HSCs transferred MHC-I molecules to LSECs and these molecules were employed for LSEC cross-presentation to CTLs. Such transfer of MHC-I molecules was sufficient to support in vivo LSEC cross-presentation of soluble antigens to CTLs. Importantly, this transfer of MHC-I molecules contributed to anti-viral CTL immunity leading to development of immune-mediated hepatitis. Conclusions Our findings demonstrate transfer of MHC-I molecules among sinusoidal liver cell populations as a potent mechanism to increase anti-viral CTL effector function. The transfer of MHC-I molecules from HSCs supplies LSECs with additional MHC-I molecules for their own cell-intrinsic cross-presentation. Such cross-allocation of MHC-I molecules in liver cell populations is distinct from cross-dressing that occurs among immune cell populations in lymphoid tissues where peptide-loaded MHC-I molecules are transferred. Our findings thus reveal a novel mechanism that increases local cross-presentation and CTL effector function in the liver, which may be instrumental for immune-surveillance during viral infection of antigen-presenting liver cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0168-8278 1600-0641
DOI:	10.1016/j.jhep.2014.04.028