title: Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance.
abstract: OBJECTIVE
  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.
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schölzel
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Schildberg
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Welz
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Börner
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Geiger
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Institute of Virology, Technische Universität München, & Helmholtz Zentrum München, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwälder
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany; Institute of Molecular Immunology, Technische Universität München, Germany. Electronic address: percy.knolle@tum.de.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Germany. Electronic address: dirk.wohlleber@uni-bonn.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wohlleber
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics*; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I / Q000235:genetics*; D055166:Hepatic Stellate Cells / Q000276:immunology* / Q000473:pathology; D007157:Immunologic Surveillance / Q000235:genetics*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal
keywords: Cross-presentation; HSC; LSEC; MHC-I