Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation
Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation
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DOI：
10.4049/jimmunol.164.7.3596
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Young, HA
中科院分区：
文献类型：
--
作者：
Hwu, P;Du, MX;Young, HA
树突状细胞(DC)在B和T淋巴细胞的激活和调节中起着关键作用，最近发现巨噬细胞产生吲哚胺2，3-双加氧酶(IDO)，通过降解色氨酸来抑制T细胞的增殖。由于DC可以来源于单核细胞，我们试图确定DC是否能够产生IDO，从而潜在地调节T细胞的增殖。对培养的人单核细胞来源的DC进行RNA的Northern印迹分析表明，CD40配体和干扰素-γ激活后可诱导IDO mRNA的表达。活化的DC产生的IDO具有功能活性，能够将色氨酸代谢为犬尿氨酸。活化的T细胞也能诱导DC产生IDO，这种作用可被抗干扰素-γ的中和性抗体抑制，DC产生IDO可抑制T细胞的增殖，这种抑制作用可被IDO抑制剂1-甲基-DL-色氨酸所阻止。这些结果表明，DC的激活诱导功能性IDO的产生，从而导致色氨酸的耗竭，从而抑制T细胞的增殖。这可能代表了DC调节免疫反应的一种潜在机制。
Dendritic cells (DCs) play a key role in the activation and regulation of B and T lymphocytes, Production of indoleamine 2,3-dioxygenase (IDO) by macrophages has recently been described to result in inhibition of T cell proliferation through tryptophan degradation. Since DCs can be derived from monocytes, we sought to determine whether DCs could produce IDO which could potentially regulate T cell proliferation. Northern blot analysis of RNA from cultured monocyte-derived human DC revealed that IDO mRNA was induced upon activation with CD40 ligand and IFN-gamma. IDO produced from activated DCs was functionally active and capable of metabolizing tryptophan to kynurenine. Activated T cells were also capable of inducing IDO production by DCs, which was inhibited by a neutralizing Ab against IFN-gamma, DC production of IDO resulted in inhibition of T cell proliferation, which could be prevented using the IDO inhibitor 1-methyl-DL-tryptophan. These results suggest that activation of DCs induces the production of functional IDO, which causes depletion of tryptophan and subsequent inhibition of T cell proliferation. This may represent a potential mechanism for DCs to regulate the immune response.