title: Modulation of immune responses after portal venous injection of antigen.
abstract: BACKGROUND
  How the localization of antigen to the liver, through means such as oral ingestion, induces tolerance is poorly understood.
  
  
  METHODS
  To elucidate potential mechanisms we used an adoptive transfer system wherein ova-specific T cells were infused into a syngeneic host, and antigen-specific T-cell responses after delivery of soluble antigen into the liver were monitored.
  
  
  RESULTS
  After infusion of antigen into the portal vein, the frequency of antigen-specific T cells in lymph nodes draining the liver was lower than the frequency in peripheral lymph nodes. These findings were the reverse of what is typically observed after subcutaneous injection of antigen with adjuvant. Infusion of antigen with adjuvant into the portal vein did not alter this pattern of antigen-specific T-cell localization; however, an increased frequency of T cells, compared with antigen alone, was observed in peripheral lymph nodes and spleen. After exposure to antigen via the portal vein, T cells isolated from lymph nodes draining the liver and challenged with antigen in vitro exhibited a diminished proliferative response compared with T cells isolated from nondraining lymph nodes. This hyporesponsiveness was not observed when the antigen was administered with adjuvant.
  
  
  CONCLUSIONS
  Our findings suggest that the influence of the liver on immune responses might reflect two processes: (1) loss of antigen-specific T cells after primary antigen injection, and (2) hyporesponsiveness on reexposure to antigen. These mechanisms may contribute to the prevention of undesirable immune responses to foods and enteric bacteria in the gastrointestinal tract. Furthermore, these results underscore the importance of minimizing inflammation in circumstances such as islet transplantation, if endogenous mechanisms of tolerance induction are to be maximized.
authors.affiliation: Department of Surgery, University of Washington, Seattle 98195, USA. lew@u.washington.edu
authors.forename: L E
authors.initials: LE
authors.lastname: Wrenshall
authors.forename: J D
authors.initials: JD
authors.lastname: Ansite
authors.forename: P M
authors.initials: PM
authors.lastname: Eckman
authors.forename: M J
authors.initials: MJ
authors.lastname: Heilman
authors.forename: R B
authors.initials: RB
authors.lastname: Stevens
authors.forename: D E
authors.initials: DE
authors.lastname: Sutherland
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance / Q000502:physiology*; D007275:Injections, Intravenous; D008099:Liver / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011169:Portal Vein; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics; D013154:Spleen; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D014018:Tissue Distribution
chemical_list: D000941:Antigens; D000939:Epitopes; D012709:Serum Albumin; D010047:Ovalbumin