Haematology Oncology Centre, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, Shandong, 250012, China.
J Clin Immunol. 2011 Aug;31(4):643-9. doi: 10.1007/s10875-011-9525-7. Epub 2011 Apr 13.
Indoleamine 2,3-dioxygenase (IDO) can promote peripheral immune tolerance and control autoimmune responses through tryptophan catabolism. Tryptophanyl-tRNA synthetase (TTS) can protect T cells from IDO-mediated cell injury. Impaired IDO-mediated tryptophan catabolism has been observed in some autoimmune diseases.
The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry.
Compared with healthy controls, the PBMCs of patients with immune thrombocytopenia (ITP) had significantly increased expressions of IDO and TTS, especially IDO. However, the plasma tryptophan concentration was significantly elevated, and kynurenine concentration was significantly reduced in ITP patients. In CD4(+) and CD8(+) T cells of the ITP patients, IDO expressions were significantly lower than those in healthy controls, but in CD19(+) and CD14(+) cells, IDO expression significantly increased. Conversely, TTS expressions in CD4(+) and CD8(+) T cells of the ITP patients were significantly higher than those in healthy controls, but there was no difference either in CD19(+) or CD14(+) cells.
These results suggest that the activity of IDO enzyme is insufficient in ITP patients. Increased TTS expressions from CD4(+) and CD8(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in ITP patients.
色氨酸 2,3-双加氧酶（IDO）可以通过色氨酸分解代谢促进外周免疫耐受和控制自身免疫反应。色氨酰-tRNA 合成酶（TTS）可以保护 T 细胞免受 IDO 介导的细胞损伤。在一些自身免疫性疾病中观察到 IDO 介导的色氨酸分解代谢受损。
采用高效液相色谱法检测血浆犬尿氨酸和色氨酸浓度。实时定量聚合酶链反应和流式细胞术分析 IDO 和 TTS 的表达。
与健康对照组相比，免疫性血小板减少症（ITP）患者的 PBMCs 中 IDO 和 TTS 的表达明显增加，尤其是 IDO。然而，ITP 患者的血浆色氨酸浓度明显升高，犬尿氨酸浓度明显降低。在 ITP 患者的 CD4(+)和 CD8(+)T 细胞中，IDO 的表达明显低于健康对照组，但在 CD19(+)和 CD14(+)细胞中，IDO 表达明显增加。相反，ITP 患者的 CD4(+)和 CD8(+)T 细胞中的 TTS 表达明显高于健康对照组，但在 CD19(+)或 CD14(+)细胞中没有差异。
这些结果表明，ITP 患者 IDO 酶的活性不足。CD4(+)和 CD8(+)T 细胞中 TTS 表达的增加可能与 ITP 患者中自身反应性 T 细胞存活增加的致病机制有关。
