Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators
Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators
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DOI：
10.1182/blood-2010-06-288498
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发表时间：
2011-02-17
期刊：
影响因子：
20.3
通讯作者：
Andersen, Mads Hald
中科院分区：
文献类型：
--
作者：
Sorensen, Rikke Baek;Hadrup, Sine Reker;Andersen, Mads Hald
吲哚胺2，3-双加氧酶（IDO）是一种免疫调节酶，在正常和病理环境中参与抑制T细胞免疫。在这里，我们描述了针对IDO的自发细胞毒性T细胞反应性不仅存在于癌症患者中，而且存在于健康人中。我们发现，这种IDO特异性CD 8（+）T细胞的存在通过消除IDO+抑制细胞来增强T细胞对病毒或肿瘤相关抗原的免疫力。这对产生白细胞介素-17（IL-17）的CD 4（+）T细胞和调节性T细胞之间的平衡产生了深远的影响。此外，这导致促炎细胞因子IL-6和肿瘤坏死因子-α的产生增加，同时减少IL-10的产生。最后，添加IDO诱导剂（即TLR 9配体胞嘧啶-磷酸-鸟苷、可溶性细胞毒性T淋巴细胞相关抗原4或干扰素γ）在癌症患者以及健康供体的外周血单核细胞中诱导IDO特异性T细胞。在临床环境中，IDO可作为免疫策略的重要且广泛适用的靶标，其中IDO发挥重要的调节作用。我们第一次描述了效应T细胞的一般调节功能，可能发挥至关重要的作用，安装或维持有效的适应性免疫反应。我们建议将这种效应T细胞称为“支持T细胞”。”（血。2011;117（7）：2200-2210）
Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8(+) T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO+ suppressive cells. This had profound effects on the balance between interleukin-17 (IL-17)-producing CD4(+) T cells and regulatory T cells. Furthermore, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-alpha while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosine-phosphate- guanosine, soluble cytotoxic T lymphocyte-associated antigen 4, or interferon gamma) induced IDO-specific T cells among peripheral blood mononuclear cells from patients with cancer as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies in which IDO plays a significant regulatory role. We describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells." (Blood. 2011;117(7):2200-2210)