title: The liver as a site of T-cell apoptosis: graveyard, or killing field?
abstract: The liver is a site at which apoptotic CD8+ cells accumulate during the clearance phase of peripheral immune responses. Normal mouse liver contains an unusual mixture of lymphocytes in which natural killer (NK) and NK-T cells are abundant and apoptotic T cells are present, and we interpret these cell populations as, respectively, agents and targets of an intrahepatic T-cell trapping and killing mechanism. In support of this idea, direct perfusion of activated lymphocyte populations through the normal liver results in the selective retention of activated CD8+ T cells. T cells trapped in this manner undergo apoptosis in the liver. This mechanism could explain the importance of the liver in oral tolerance, the phenomenon of tolerance induced by portal vein infusion of antigenic cells, the tolerance to allogeneic liver allografts, and the persistence of some liver pathogens including hepatitis C.
authors.affiliation: Immunobiology Section, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA. nick.crispe@yale.edu
authors.forename: I N
authors.initials: IN
authors.lastname: Crispe
authors.forename: T
authors.initials: T
authors.lastname: Dao
authors.forename: K
authors.initials: K
authors.lastname: Klugewitz
authors.forename: W Z
authors.initials: WZ
authors.lastname: Mehal
authors.forename: D P
authors.initials: DP
authors.lastname: Metz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016130:Immunophenotyping; D007408:Intestinal Absorption; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008102:Liver Circulation; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011169:Portal Vein; D019014:fas Receptor / Q000276:immunology
chemical_list: D000941:Antigens; D019014:fas Receptor