title: Inhibition of inflammatory CD4 T cell activity by murine liver sinusoidal endothelial cells.
abstract: OBJECTIVE
  The liver can mitigate the inflammatory activity of infiltrating T cells by mechanisms that are not entirely clear. Here we investigated the role of liver sinusoidal endothelial cells (LSECs) in regulating the activity of inflammatory CD4 T cells.
  
  
  METHODS
  Interactions between T helper (Th) 1 or Th17 cells and LSEC were studied by intravital microscopy and by in vitro stimulation assays.
  
  
  RESULTS
  Circulating CD4 T cells established lasting and repeated interactions with liver endothelium in vivo. Stimulation of Th1 and Th17 cells by LSEC greatly inhibited their capacity to secrete interferon-γ or interleukin-17 in vitro; in contrast, stimulation by dendritic cells (DCs) resulted in considerable secretion of both cytokines. Cytokine release by Th1 or Th17 cells seemed to be actively suppressed by LSEC, as indicated by the inhibition of cytokine secretion even in the presence of Th1- and Th17-promoting DC. This inhibition of CD4 T cell effector function seemed to depend on the dominance of inhibitory over activating co-stimulatory signals on LSEC, since (1) cytokine secretion could be restored by increased CD28 co-activation; (2) LSEC from interleukin-10(-/-) mice, which manifest increased activating signals, such as MHC II, and decreased inhibitory signals, such as PD-L1, failed to suppress cytokine secretion; and (3) cytokine secretion by Th1 or Th17 cells that lacked PD-1, the ligand for inhibitory PD-L1, could not be suppressed by LSEC.
  
  
  CONCLUSIONS
  LSEC inhibit inflammatory cytokine secretion of Th1 and Th17 effector CD4 T cells in dependence of interleukin-10 and PD-1.
authors.affiliation: Department of Medicine I, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Antonella
authors.initials: A
authors.lastname: Carambia
authors.forename: Christian
authors.initials: C
authors.lastname: Frenzel
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Bruns
authors.forename: Dorothee
authors.initials: D
authors.lastname: Schwinge
authors.forename: Rudolph
authors.initials: R
authors.lastname: Reimer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hohenberg
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.forename: Christoph
authors.initials: C
authors.lastname: Schramm
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.forename: Johannes
authors.initials: J
authors.lastname: Herkel
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10