Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells
Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells
复制标题
DOI：
10.1182/blood-2004-06-2089
复制
发表时间：
2005-02-15
期刊：
影响因子：
20.3
通讯作者：
Shearer, GM
中科院分区：
文献类型：
--
作者：
Boasso, A;Herbeuval, JP;Shearer, GM
吲哚胺-2，3-双加氧酶（IDO）和色氨酸-tRNA-合成酶（TTS）是干扰素-γ（IFN-γ）诱导的酶，分别负责色氨酸降解和其在蛋白质合成中的用途。IFN-γ诱导的IDO在鼠和人模型中具有免疫调节特性。已经假设TTS的伴随增加保护IDO表达细胞免受色氨酸催化。IDO可由重组可溶性细胞毒性T淋巴细胞抗原-4（CTLA-4-Fc）在树突状细胞（DC）中诱导。我们研究了CTLA-4-Fc对人外周血单个核细胞（PBMC）和分离的白细胞亚群中IDO和TTS mRNA表达的影响。CTLA-4-Fc暴露诱导未分离的PBMC以及单核细胞衍生的成熟Ms. CTLA-4-Fc处理的PBMC中分离的CD 4（+）T细胞中IDO和TTS表达增加，与未处理的细胞相比，显示IDO和TTS增加。来自CTLA-4-Fc处理的PBMC的CD 8（+）T细胞表达增加的TTS水平，但不表达IDO。用CTLA-4-Fc预处理PBMC可抑制流感病毒（Flu）或植物血凝素A（PHA）诱导的CD 4（+）T细胞活化，但对CD 8（+）T细胞无影响。这是第一份关于人CD 4（+）和CD 8（+）T细胞中CTLA-4-B7系统对IDO和TTS调节的报告，并提出了这两种调节酶为调节免疫应答提供重要机制的可能性。(C)2005年美国血液学会。
Indoleamine-2,3-dioxygenase (IDO) and tryptophanyl-tRNA-synthetase (TTS) are interferon-gamma (IFN-gamma)-inducible enzymes that are responsible for tryptophan degradation and for its use in protein synthesis, respectively. IFN-gamma-induced IDO has immunomodulatory properties in murine and human models. A concomitant increase of TTS has been postulated to protect the IDO-expressing cells from tryptophan catabolism. IDO can be induced in dendritic cells (DCs) by recombinant soluble cytotoxic T lymphocyte antigen-4 (CTLA-4-Fc). We investigated the effects of CTLA-4-Fc on IDO and TTS mRNA expression in human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte subsets. CTLA-4-Fc exposure induced increased IDO and TTS expression in unseparated PBMCs, as well as in monocyte-derived mature Ms. CD4(+) T cells isolated from CTLA-4-Fc-treated PBMCs showed increased IDO and TTS compared with untreated cells. CD8(+) T cells from CTLA-4-Fc-treated PBMCs expressed increased levels of TTS but not IDO. Pretreatment of PBMCs with CTLA-4-Fc inhibited the activation of CD4(+) T cells induced by influenza A virus (Flu) or phytohemagglutinin A (PHA), but had no effect on CD8(+) T cells. This is the first report of IDO and TTS regulation by the CTLA-4-B7 system in human CD4(+) and CD8(+) T cells, and raises the possibility that these 2 tryptophan-modulating enzymes provide an important mechanism for regulating immune responses. (C) 2005 by The American Society of Hematology.