Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation
Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation
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DOI：
10.1182/blood-2003-11-3909
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发表时间：
2004-06-15
期刊：
影响因子：
20.3
通讯作者：
Dilloo, D
中科院分区：
文献类型：
--
作者：
Meisel, R;Zibert, A;Dilloo, D
骨髓基质细胞（MSCs）抑制同种异体T细胞反应，但介导这种免疫抑制作用的MSCs的分子机制仍然存在争议。最近，吲哚胺2，3-双加氧酶（IDO）的表达（其由干扰素-γ（IFN-γ）诱导并催化从色氨酸转化为犬尿氨酸）已被鉴定为专职抗原呈递细胞中的T细胞抑制性效应子途径。在这里，我们表明，人MSC表达IDO蛋白，并表现出功能性IDO活性与IFN-γ刺激后。MSC抑制混合淋巴细胞反应（MLR）中的同种异体T细胞应答。伴随地，在MSC/MLR共培养上清液中检测到导致色氨酸消耗和犬尿氨酸产生的IDO活性。色氨酸的添加显著恢复同种异体T细胞增殖，从而鉴定IDO介导的色氨酸催化剂作为人MSC中的新型T细胞抑制效应器机制。由于IDO介导的T细胞抑制依赖于MSC活化，因此IDO活性的调节可能会改变MSC在不同治疗应用中的免疫抑制特性。(C)2004年，美国血液学会。
Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN-gamma. MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications. (C) 2004 by The American Society of Hematology.