title: Human hepatic stellate cells inhibit T-cell response through B7-H1 pathway.
abstract: BACKGROUND
  The liver is an immunologic privileged organ; liver allografts are accepted across major histocompatibility complex barriers in many species. However, hepatocyte transplants are acutely rejected, suggesting a role for liver nonparenchymal cells in regulating the immunoresponse. We have shown potent immunoregulatory activity of hepatic stellate cells (HSCs) in mice. The aim of this study was to examine the immunoregulatory activity of human HSCs.
  
  
  METHODS
  HSCs were isolated from normal human livers for analyses of their impact on T-cell response.
  
  
  RESULTS
  HSCs expressed low HLA-DR and costimulatory molecules CD40 and CD80 but constitutively expressed high levels of CD54. Interferon-γ stimulated HSCs to express B7-H1 in a dose-dependent manner and produce the suppressive cytokines interleukin-6, interleukin-10, and transforming growth factor-β but did not affect expression of HLA-DR, CD40, and CD80. Human HSCs did not stimulate allogeneic T-cell proliferative response, indicating that they are not professional antigen-presenting cells. HSCs markedly inhibited T-cell response elicited by either allogeneic antigen-presenting cells or CD3/CD28 beads, which was associated with increases in activated CD4 and CD8 T-cell apoptosis. Addition of anti-B7-H1 blocking antibody significantly reversed the inhibitory effect.
  
  
  CONCLUSIONS
  Human HSCs demonstrate potent immunoregulatory activity via B7-H1-mediated induction of apoptosis in activated T cells. Understanding of the involved mechanisms may lead to development of novel therapeutic approaches for treatment of liver diseases.
authors.affiliation: Department of General Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44147, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Charles
authors.forename: Hong-Shiue
authors.initials: HS
authors.lastname: Chou
authors.forename: Lianfu
authors.initials: L
authors.lastname: Wang
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Shiguang
authors.initials: S
authors.lastname: Qian
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D019013:CD40 Antigens; D018799:Intercellular Adhesion Molecule-1