title: IFN-gamma is an absolute requirement for spontaneous acceptance of liver allografts.
abstract: Experimental liver allografts undergo spontaneous acceptance despite undergoing rejection during the first few weeks post transplant. We explored the role of interferon-gamma (IFN-gamma) in the spontaneous acceptance of mouse liver allografts. Strain of mouse (CBA) liver allografts transplanted into normal BALB/c mice developed histologic changes typical of rejection that spontaneously regressed, permitting long-term survival of these allografts similar to that of syngeneic grafts. In contrast, CBA liver allografts in IFN-gamma-deficient hosts manifested not only infiltration but also hemorrhage and necrosis, with no survival beyond 14 days. Despite differences in survival, local expression of cytotoxic T-cell genes in the transplant was not increased in IFN-gamma-deficient hosts, but livers in interferon-gamma-deficient mice (GKO) hosts displayed much less induction of major histocompatibility complex (MHC) class I and II expression. To determine whether the difference in survival was secondary to the direct effects of IFN-gamma on the liver, we transplanted livers from IFN-gamma-receptor-deficient mice into normal hosts. Liver allografts lacking IFN-gamma receptors also developed hemorrhage and necrosis with minimal induction of MHC expression. Thus IFN-gamma mediates a direct effect on rejecting liver allografts that reduces hemorrhage and necrosis, induces MHC expression, and is absolutely required for spontaneous acceptance.
authors.affiliation: Departments of Surgery, Medicine, Laboratory Medicine and Pathology, and Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: Tina S
authors.initials: TS
authors.lastname: Mele
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kneteman
authors.forename: Lin-Fu
authors.initials: LF
authors.lastname: Zhu
authors.forename: Vido
authors.initials: V
authors.lastname: Ramassar
authors.forename: Joan
authors.initials: J
authors.lastname: Urmson
authors.forename: Brendan
authors.initials: B
authors.lastname: Halloran
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Churchill
authors.forename: Lawrence
authors.initials: L
authors.lastname: Jewell
authors.forename: Kevin
authors.initials: K
authors.lastname: Kane
authors.forename: Philip F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000818:Animals; D017931:DNA Primers; D020869:Gene Expression Profiling; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma