title: Blocking indoleamine dioxygenase activity early after rat liver transplantation prevents long-term survival but does not cause acute rejection.
abstract: In a well-characterized rat model of liver transplantation, Piebald Virol Glaxo strain livers are accepted long term in fully mismatched Dark Agouti recipients (tolerance; TOL), but rejected in Lewis recipients (rejection; REJ). Spontaneous tolerance induction is associated with increased interferon-gamma expression, and we examined the role of the interferon-gamma-inducible immunomodulatory enzyme indoleamine dioxygenase (IDO) in this model. On day 3 after transplantation, IDO expression in the spleen of TOL recipients was significantly greater than in REJ. The B-cell population accounted for this early IDO increase. Intragraft expression of IDO increased to the same extent in both TOL and REJ. IDO inhibition for 7 days after transplantation reduced survival, but did not cause acute rejection of the liver in the TOL model. In conclusion, the differential IDO expression by B lymphocytes in the spleen of TOL recipients is not critical for preventing acute rejection.
authors.affiliation: Collaborative Transplantation Research Group, Bosch Institute, Royal Prince Alfred Hospital, University of Sydney, Australia.
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Laurence
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Wang
authors.forename: Euiyoun T
authors.initials: ET
authors.lastname: Park
authors.forename: Alexandra
authors.initials: A
authors.lastname: Buchanan
authors.forename: Andrew
authors.initials: A
authors.lastname: Clouston
authors.forename: Richard D M
authors.initials: RD
authors.lastname: Allen
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Mccaughan
authors.forename: G Alex
authors.initials: GA
authors.lastname: Bishop
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Sharland
mesh_terms: D000818:Animals; D002469:Cell Separation; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000502:physiology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase