Immunological role of indoleamine 2,3-dioxygenase in rat liver allograft rejection and tolerance.
OBJECTIVE
Indoleamine 2,3-dioxygenase (IDO) is expressed in the placenta and plays an essential role in maternal tolerance. Recent data showed that giving IDO inhibitor blocked liver allograft tolerance. However, the immunological role of IDO in rat liver allograft models has not been characterized. In the present study, the time-course of IDO expression and the localization of IDO were analyzed to address the role of IDO in the induction of tolerance.


METHODS
Rat orthotopic liver transplantations (OLT) were performed and IDO gene expression of OLT livers was analyzed. Immunohistochemistry was used to evaluate the localization of IDO-expressed cells in the liver.


RESULTS
The IDO gene was detected in the allogeneic liver graft at the acute phase but the signal could not be detected when these OLT rats were treated with cyclosporinee A. The time-course of IDO gene expression in liver grafts of the spontaneous tolerant OLT model revealed that the IDO mRNA was expressed in both the rejection phase and the induction phase of tolerance, but the signal was gradually lowered during the maintenance phase of tolerance. Immunohistochemistry confirmed that the IDO protein was detected in antigen-presenting cells but not in hepatocytes.


CONCLUSIONS
Our results demonstrated that IDO is induced in antigen-presenting cells of rat liver allografts under drug-free status, suggesting that indirect or direct recognition of donor antigen and further T-cell activation may be inhibited. IDO may act as a local immunosuppressive molecule to protect transplanted cells, tissues and organs from immune attack.
Lin
Yu-Chun
YC
Department of Biological Science, Developmental Biology Laboratory, Graduate School of Science, Hiroshima University, Hiroshima, Japan. kcgmh.livertx@msa.hinet.net
Chen
Chao-Long
CL
Nakano
Toshiaki
T
Goto
Shigeru
S
Kao
Ying-Hsien
YH
Hsu
Li-Wen
LW
Lai
Chia-Yun
CY
Jawan
Bruno
B
Cheng
Yu-Fan
YF
Tateno
Chise
C
Yoshizato
Katsutoshi
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D007108:Immune Tolerance / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D016572:Cyclosporine