title: Induction of immune hyporesponsiveness after portal vein immunization with ovalbumin.
abstract: BACKGROUND
  Previous work has demonstrated prolonged allograft survival after donor-specific portal vein immunization before the transplantation. The purpose of this study was to examine the potential mechanism of portal vein-induced hyporesponsiveness after portal vein immunization with the soluble protein ovalbumin.
  
  
  METHODS
  Balb/c mice were immunized with a portal vein injection of ovalbumin. After the immunization, in vivo delayed-type hypersensitivity response and in vitro proliferative response of ovalbumin-specific T cells were assessed to determine host immune response. Type 1 (IL-2, IL-12, IFN-gamma) and type 2 (IL-4, TGF-beta) regulatory cytokines were assessed by semiquantitative reverse transcriptase polymerase chain reaction. Sera anti-ovalbumin IgG, IgG1, and IgG2a were measured by enzyme-linked immunosorbent assay, and the antigen-presenting ability of liver nonparenchymal cells (NPCs) was assessed by T-cell proliferation to ovalbumin in vitro.
  
  
  RESULTS
  There was significant inhibition of ovalbumin-specific delayed-type hypersensitivity and T-cell proliferation in portal vein-immunized mice compared with intraperitoneal-immunized or control mice. Reverse transcriptase polymerase chain reaction analysis results showed that lymphocytes from portal vein-immunized mice exhibited decreased type 1 and increased type 2 cytokine messenger RNA expression compared with intraperitoneal-immunized or control animals. The type 2 cytokine response of lymphocytes from ovalbumin portal vein-immunized mice correlated with increased sera ovalbumin-IgG1 and decreased IgG2a. The results of an antigen-presenting assay revealed that liver NPCs were deficient antigen-presenting cells compared with adherent cells from heart or spleen.
  
  
  CONCLUSIONS
  Processing of ovalbumin by hepatic NPCs results in hyporesponsiveness to ovalbumin by an impaired type 1 cytokine response and a preferential shift toward a type 2 cytokine response, possibly because of defective antigen presentation by hepatic NPCs. Intrahepatic processing of antigen may play an important role in the development of strategies to reduce host immunoreactivity against transplanted allografts.
authors.affiliation: Department of Surgery, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: C R
authors.initials: CR
authors.lastname: Ong
authors.forename: G J
authors.initials: GJ
authors.lastname: McKenna
authors.forename: A L
authors.initials: AL
authors.lastname: Mui
authors.forename: R M
authors.initials: RM
authors.lastname: Smith
authors.forename: S W
authors.initials: SW
authors.lastname: Chung
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D016207:Cytokines / Q000235:genetics; D005260:Female; D006082:Graft Enhancement, Immunologic; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D011169:Portal Vein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D010047:Ovalbumin