title: Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity.
abstract: OBJECTIVE
  Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8(+) T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8(+) T-cell activation upon such stimulation.
  
  
  METHODS
  Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo relevance of the findings was confirmed with bone-marrow chimeric animals.
  
  
  RESULTS
  LSECs expressed numerous pattern recognition receptors that allowed for sentinel function, but ligand-induced activation of these receptors was not sufficient to overcome tolerance induction of CD8(+) T cells. Importantly, viral infection with murine cytomegalovirus caused functional maturation of antigen-presenting LSECs and was sufficient to promote antigen-specific differentiation into effector CD8(+) T cells in the absence of dendritic cells and independent of CD80/86.
  
  
  CONCLUSIONS
  These results shed new light on the generation of organ-specific immunity and may contribute to overcoming tolerance in relevant situations, such as cancer.
authors.affiliation: Institute of Molecular Medicine, University of Bonn, Bonn, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kern
authors.forename: Alexey
authors.initials: A
authors.lastname: Popov
authors.forename: Kai
authors.initials: K
authors.lastname: Scholz
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schumak
authors.forename: Dominik
authors.initials: D
authors.lastname: Djandji
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Daniela
authors.initials: D
authors.lastname: Eggle
authors.forename: Torsten
authors.initials: T
authors.lastname: Sacher
authors.forename: Rainer
authors.initials: R
authors.lastname: Zawatzky
authors.forename: Rafaela
authors.initials: R
authors.lastname: Holtappels
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey-Pascher
authors.forename: Linda
authors.initials: L
authors.lastname: Diehl
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koszinowski
authors.forename: Joachim
authors.initials: J
authors.lastname: Schultze
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002678:Chimera; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000821:virology*; D051379:Mice; D018146:Muromegalovirus; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D008024:Ligands; D051192:Receptors, Pattern Recognition