吲哚胺2，3双加氧酶在丁酸钠诱导未成熟树突状细胞介导T细胞无能的机制

The role of IDO in T cell anergy of sodium butyrate-induced immature

目的 观察吲哚胺2，3双加氧酶（IDO）在丁酸钠诱导不成熟树突状细胞（DC）抑制T细胞免疫反应中的作用。方法通过粒细胞-巨噬细胞集落刺激因子（GM—CSF）和白细胞介素（IL）-4体外诱导人外周血来源的DC，第6天加入丁酸钠和不同促成熟因子继续诱导DC分化，逆转录-聚合酶链反应（RT—PCR）、Real-timePCR检测各组IDOmRNA的表达。混合淋巴细胞反应检测各组刺激T细胞增殖能力，进一步在丁酸钠组和对照组分别加入IDO的阻断剂1-甲基色氨酸（1-MT）后了解对T细胞增殖能力的改变。结果RT—PCR结果显示丁酸钠组DCIDOmRNA表达量（0．84±0．01）高于对照组（0．55±0．01）及脂多糖（LPS，0．53±0．01）等诱导成熟组。Real—timePCR进一步显示与对照组比较，丁酸钠组IDOmRNA的表达升高了约（32．03±4．01）倍。MLR显示丁酸钠组DC刺激淋巴细胞增殖指数（1．53±1．0）低于LPS（9．87±3．8）等成熟组DC，并且采用IDO的抑制剂1-MT可以降低抑制T细胞增殖的能力。结论丁酸钠诱导下DC可能通过IDO途径降解细胞微环境中的色氨酸来发挥对T细胞增殖的抑制作用。

Objective To investigate the role of indoleamine 2,3-dioxygense （IDO） in T cell an- ergy of the immature dendritic cells （DCs） induced by sodium butyrate. Methods Human monocyte-derived immature DCs were induced with granuloeyte macrophage-eolony stimulating factor （GM-CSF） and interleukin-4 （IL-4）, and divided into 5 groups on the 6th day. Trizol was added to extract total RNA of each group after 24-h induction. IDO mRNA expression was detected by RT-PCR and real-time PCR. 1- methyl-tryptophan （1-MT） was also used to test mixed lymphocyte reaction in sodium butyrate-induced DCs. Cells were harvested after 96-h incubation and fluorescence intensity was detected by FCM. Results IDO mRNA expression in sodium butyrate group was significantly higher （0.84 ±0.01 ） than control group （0.55± 0.01 ） and other mature groups （0.53 ± 0.01 ） by RT-PCR. The result was further confirmed by real-time PCR. In comparison with the control group, the IDO mRNA expression of DCs was increased by （32.03±4.01 ） fold. The proliferation of lymphoeytes was increased in sodium butyrate group with 1-MT by FCM ,which suggested 1-MT may antagonize the inhibition of sodium butyrate-induced lymphocyte proliferation. Conclusion Sodium butyrate may inhibit the lymphocyte proliferation by IDO that can degradate amino-indole propionic acid in microenvironment.