Curreli S, Romerio F, Mirandola P, Barion P, Bemis K, Zella D
Institute of Human Virology, University of Maryland Biotechnology Institute (UMBI), Baltimore, MD 20201, USA.
J Interferon Cytokine Res. 2001 Jun;21(6):431-7. doi: 10.1089/107999001750277916.
Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the catabolism of tryptophan. By creating a local microenvironment in which levels of tryptophan are low, IDO-expressing antigen-presenting cells (APC) could regulate T cell activation. This may be relevant to control both viral and bacterial replication as well as neoplastic cell growth. Interferon-alpha (IFN-alpha) is an antiviral cytokine affecting cellular differentiation. In addition, it reduces proliferation of CD4(+) T cells by several molecular mechanisms. To dissect the molecular steps responsible for the INF-mediated antiproliferative activity, we sought to determine whether activated primary CD4(+) T cells in the presence of IFN-alpha would produce IDO. We demonstrate here that IDO mRNA is not present in resting CD4(+) T cells. Stimulation with anti-CD3 plus interleukin-2 (IL-2) induces expression of IDO mRNA (about 2000 copies/150,000 cells), as determined by semiquantitative RT-PCR. When cells were stimulated in the presence of IFN-alpha, expression of IDO mRNA was significantly increased (more than 12,000 copies/150,000 cells). Functional analysis of IDO activity paralleled the results obtained with RT-PCR, demonstrating increased production of active enzyme in CD4(+) T cells stimulated in the presence of IFN-alpha. Our results indicate that IFN-alpha modulates levels of IDO produced by activated CD4(+) T cells. This would likely affect bystander cells by modifying levels of tryptophan in the local microenvironment.
吲哚胺2,3-双加氧酶（IDO）是色氨酸分解代谢中的限速酶。通过营造一种色氨酸水平较低的局部微环境，表达IDO的抗原呈递细胞（APC）可调节T细胞活化。这可能与控制病毒和细菌复制以及肿瘤细胞生长都有关。干扰素-α（IFN-α）是一种影响细胞分化的抗病毒细胞因子。此外，它通过多种分子机制降低CD4(+) T细胞的增殖。为了剖析负责INF介导的抗增殖活性的分子步骤，我们试图确定在IFN-α存在的情况下活化的原代CD4(+) T细胞是否会产生IDO。我们在此证明，静息CD4(+) T细胞中不存在IDO mRNA。通过半定量逆转录聚合酶链反应（RT-PCR）测定，用抗CD3加白细胞介素-2（IL-2）刺激可诱导IDO mRNA表达（约2000拷贝/150,000个细胞）。当细胞在IFN-α存在的情况下受到刺激时，IDO mRNA的表达显著增加（超过12,000拷贝/150,000个细胞）。IDO活性的功能分析与RT-PCR结果一致，表明在IFN-α存在的情况下受到刺激的CD4(+) T细胞中活性酶的产生增加。我们的结果表明，IFN-α可调节活化的CD4(+) T细胞产生的IDO水平。这可能会通过改变局部微环境中色氨酸的水平来影响旁观者细胞。
