Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Feb 7, 2010; 16(5): 636-640
Published online Feb 7, 2010. doi: 10.3748/wjg.v16.i5.636
Inhibition of allogeneic T-cell response by Kupffer cells expressing indoleamine 2,3-dioxygenase
Mao-Lin Yan, Yao-Dong Wang, Yi-Feng Tian, Zhi-De Lai, Lv-Nan Yan
Mao-Lin Yan, Yao-Dong Wang, Yi-Feng Tian, Zhi-De Lai, Lv-Nan Yan, Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
Author contributions: Yan ML and Yan LN designed the study; Yan ML, Yan LN, Tian YF and Lai ZD performed the experiments and the data analysis; Yan ML wrote the manuscript; Wang YD and Yan LN revised the manuscript.
Supported by Natural Science Foundation of Fujian Province, No. 2007J0073; Young Talents Innovation Foundation of Fujian Province, No. 2006F3033
Correspondence to: Mao-Lin Yan, MD, Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China. yanmaolin74@163.com
Telephone: +86-591-87552554 Fax: +86-591-87552554
Received: October 18, 2009
Revised: December 4, 2009
Accepted: December 11, 2009
Published online: February 7, 2010
Abstract

AIM: To explore the possibility and mechanism of inhibiting allogeneic T-cell responses by Kupffer cells (KC) pretreated with interferon-γ (IFN-γ) in vitro.

METHODS: The expressions of indoleamine 2,3-dioxygenase (IDO) mRNA and FasL mRNA in KC pretreated with IFN-γ 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 [3H] 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-γ, 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.

Keywords: Kupffer cell; FasL; Indoleamine 2,3-dioxygenase; T-cell proliferation