IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-γ increase in normal pregnancy but decrease in spontaneous abortion
IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-γ increase in normal pregnancy but decrease in spontaneous abortion
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DOI：
10.1093/molehr/gah246
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发表时间：
2005-12-01
影响因子：
4
通讯作者：
Saito, S
中科院分区：
文献类型：
--
作者：
Miwa, N;Hayakawa, S;Saito, S
最近的数据表明，CD4(+)CD25(+)调节性T细胞(Treg)和一种名为吲哚胺2，3-双加氧酶(IDO)的酶介导了母体对胎儿的耐受。有趣的是，Treg细胞在其表面表达CTLA-4分子，并且CTLA-4连接B7(CD80/86)通过诱导产生干扰素-γ来增强树突状细胞(DC)和单核细胞的IDO活性。本研究采用流式细胞术检测了CTLA-4/Fc融合蛋白或干扰素-γ作用于外周血单核细胞和蜕膜单核细胞或DC后IDO的表达。正常妊娠时外周血DC、蜕膜DC和单核细胞上IDO的表达均上调。而自然流产患者经干扰素-γ或CTLA-4处理后，DC和单核细胞上IDO的表达均降低。自然流产组外周血、蜕膜单核细胞和DC的CD86表达均低于正常妊娠组。自然流产患者经CTLA-4/FC治疗后，蜕膜和外周血单个核细胞产生的干扰素-γ水平明显低于正常妊娠组。这些数据表明，Treg细胞上的CTLA-4通过诱导干扰素-γ的产生，上调蜕膜和外周血树突状细胞和单核细胞上IDO的表达。
Recent data demonstrated that CD4(+)CD25(+) regulatory T (Treg) cells and an enzyme called indoleamine 2,3-dioxygenase (IDO) mediate maternal tolerance to the fetus. Interestingly, Treg cells express the CTLA-4 molecule on their surface, and B7 (CD80/86) ligation by CTLA-4 enhanced IDO activity of dendritic cells (DCs) and monocytes by the induction of interferon gamma (IFN-gamma) production. In this study, we studied the IDO expression on peripheral blood monocytes and decidual monocytes or DCs after treatment with CTLA-4/Fc fusion protein or IFN-gamma using flow cytometry. IDO expressions on both peripheral blood DC and decidual DC and monocytes were up-regulated during normal pregnancy. On the other hand, both IDO expression on DC and monocytes after IFN-gamma treatment or CTLA-4 treatment were decreased in spontaneous abortion cases. The expression of CD86 on peripheral blood and decidual monocytes and DC in spontaneous abortion cases was lower compared with those in normal pregnancy subjects. Also, IFN-gamma production by decidual and peripheral blood mononuclear cells after CTLA-4/Fc treatment in spontaneous abortion cases was significantly lower than those in normal pregnancy subjects. These data suggest that CTLA-4 on Treg cells up-regulates IDO expression on decidual and peripheral blood DC and monocytes by the induction of IFN-gamma production.