Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia and IRCCS San Matteo Foundation, Via Taramelli 5, Pavia, Italy.
J Heart Lung Transplant. 2009 Nov;28(11):1185-92. doi: 10.1016/j.healun.2009.07.023. Epub 2009 Sep 26.
Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the degradation of tryptophan (Try) to kynurenine (Kyn), is thought to suppress T-cell activity. Although a few experimental studies have suggested a role for IDO in graft acceptance, human data are scarce and inconclusive. We sought to establish whether, in lung transplant recipients (LTRs), plasma IDO activity mirrors the level of graft acceptance.
We measured the plasma Kyn/Try ratio, reflecting IDO activity, by high-performance liquid chromatography (HPLC) in 90 LTRs, including 26 patients who were still functionally/clinically stable for >36 post-transplant months (stable LTRs) and 64 LTRs with bronchiolitis obliterans syndrome (BOS, Grades 0-p to 3). Twenty-four normal healthy controls (NHCs) were also included.
The Kyn/Try ratio in stable LTRs resembled that observed in NHCs, whereas, unexpectedly, patients with BOS, who had lower counts of peripheral CD4(+) T-regulatory cells and tolerogenic plasmacytoid dendritic cells than stable LTRs, showed an increased plasma Kyn/Try ratio compared with both NHCs and stable LTRs. IDO expression by in vitro-stimulated peripheral blood mononuclear cells (PBMC) did not vary between BOS and stable LTRs. Furthermore, BOS patients displayed signs of chronic systemic inflammation (increased plasma levels of interleukin-8 and tumor necrosis factor-alpha) and higher T-cell activation (increased frequency of peripheral interferon-gamma-producing clones).
Our results suggest that, in vivo, in lung transplantation, plasma IDO activity does not reflect the degree of lung graft acceptance, but instead is correlated with the degree of chronic inflammation.
色氨酸（Try）降解为犬尿氨酸（Kyn）所涉及的酶吲哚胺 2,3-双加氧酶（IDO）被认为可抑制 T 细胞活性。虽然一些实验研究提示 IDO 在移植物接受中起作用，但人体数据稀少且不确定。我们试图确定 IDO 活性是否可反映肺移植受者（LTR）中肺移植物的接受程度。
我们通过高效液相色谱法（HPLC）检测了 90 例 LTR 血浆中的犬尿氨酸/色氨酸比值（Kyn/Try），该比值反映了 IDO 活性。这 90 例 LTR 包括 26 例移植后 36 个月以上仍功能/临床稳定的患者（稳定 LTR）和 64 例有细支气管炎性闭塞综合征（BOS，0-p 至 3 级）的患者。还纳入了 24 例正常健康对照者（NHC）。
稳定 LTR 的 Kyn/Try 比值与 NHC 观察到的相似，而令人意外的是，与稳定 LTR 相比，BOS 患者外周血 CD4+调节性 T 细胞和耐受性浆细胞样树突状细胞计数较低，但其血浆 Kyn/Try 比值升高，与 NHC 和稳定 LTR 相比均升高。体外刺激的外周血单核细胞（PBMC）的 IDO 表达在 BOS 和稳定 LTR 之间无差异。此外，BOS 患者表现出慢性全身炎症的迹象（白细胞介素-8 和肿瘤坏死因子-α的血浆水平升高）和更高的 T 细胞激活（外周产生干扰素-γ的克隆的频率增加）。
我们的结果提示，在肺移植中，体内 IDO 活性与肺移植物的接受程度无关，而与慢性炎症程度相关。
