Blocking indoleamine dioxygenase activity early after rat liver transplantation prevents long-term survival but does not cause acute rejection.
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.
Laurence
Jerome M
JM
Collaborative Transplantation Research Group, Bosch Institute, Royal Prince Alfred Hospital, University of Sydney, Australia.
Wang
Chuanmin
C
Park
Euiyoun T
ET
Buchanan
Alexandra
A
Clouston
Andrew
A
Allen
Richard D M
RD
Mccaughan
Geoffrey W
GW
Bishop
G Alex
GA
Sharland
Alexandra F
AF
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
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase