Inhibition of allogeneic T-cell response by Kupffer cells expressing indoleamine 2,3-dioxygenase.
OBJECTIVE
To explore the possibility and mechanism of inhibiting allogeneic T-cell responses by Kupffer cells (KC) pretreated with interferon-gamma (IFN-gamma) in vitro.


METHODS
The expressions of indoleamine 2,3-dioxygenase (IDO) mRNA and FasL mRNA in KC pretreated with IFN-gamma were studied with real-time polymerase chain reaction (PCR). The catabolism of tryptophan by IDO from KC was analyzed by high performance liquid chromatography. Allogeneic T-cell response was used to confirm the inhibition of KC in vitro. The proliferation of lymphocytes was detected using [(3)H] thymidine incorporation. Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay.


RESULTS
Real-time PCR revealed IDO mRNA and FasL mRNA expressions in KC pretreated with IFN-gamma, and IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KC expressing IDO and FasL in BABL/c mice acquired the ability to suppress the proliferation of T-cells from C57BL/6, which could be blocked by addition of 1-methyl-tryptophan and anti-FasL antibody. KC expressing IDO could induce allogeneic T-cell apoptosis.


CONCLUSIONS
In addition to Fas/FasL pathway, IDO may be another mechanism for KC to induce immune tolerance.
Yan
Mao-Lin
ML
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China. yanmaolin74@163.com
Wang
Yao-Dong
YD
Tian
Yi-Feng
YF
Lai
Zhi-De
ZD
Yan
Lv-Nan
LN
D000818:Animals; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance / Q000502:physiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007728:Kupffer Cells / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D014364:Tryptophan / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014364:Tryptophan