Inhibition of allogeneic T-cell response by Kupffer cells expressing indoleamine 2,3-dioxygenase.

AIM

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.

CONCLUSION

In addition to Fas/FasL pathway, IDO may be another mechanism for KC to induce immune tolerance.