Li Huiyuan, Hao Yating, Zhang Donglei, Liu Wenjie, Li Yang, Lyu Mingen, Fu Rongfeng, Xue Feng, Liu Xiaofan, Yang Renchi
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Br J Haematol. 2017 Jul;178(2):292-301. doi: 10.1111/bjh.14661. Epub 2017 May 3.
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8 CD28 suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8 CD28 CD127 proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8 CD28 Ts cells in ITP patients was impaired. Mechanistic studies have shown that CD8 CD28 Ts cells from controls can downregulate CD80 and upregulate LILRB4 (ITL3) and LILRB2 (ILT4) expression on CD14 monocytes, whereas these abilities were not found in Ts cells from ITP patients. Furthermore, Inducible T-cell costimulatory (ICOS) expression on the Ts cell surface after activation was decreased whereas programmed death 1 and interleukin 10 expression was not changed in ITP patients compared with those of controls. In summary, the down-regulated quantity and function of Ts cells in active patients indicated that a Ts defect was involved in ITP. Moreover, decreased ICOS expression and the loss of the ability to regulate co-stimulator expression on antigen-presenting cells partly explained the defective Ts-mediated suppression.
原发性免疫性血小板减少症（ITP）是一种获得性自身免疫性疾病，免疫耐受的丧失与ITP的发病机制有关。CD8 CD28抑制性（Ts）细胞具有免疫抑制功能，并参与多种自身免疫性疾病。然而，Ts细胞在ITP中的作用目前尚不清楚。在此，采用流式细胞术检测CD8 CD28 CD127比例，结果显示活动期ITP患者的该比例低于对照组。功能分析表明，ITP患者中CD8 CD28 Ts细胞的免疫抑制功能受损。机制研究表明，对照组的CD8 CD28 Ts细胞可下调CD14单核细胞上的CD80，并上调LILRB4（ITL3）和LILRB2（ILT4）的表达，而ITP患者的Ts细胞则未发现这些能力。此外，与对照组相比，ITP患者激活后Ts细胞表面的诱导性T细胞共刺激分子（ICOS）表达降低，而程序性死亡蛋白1和白细胞介素10的表达未发生变化。总之，活动期患者中Ts细胞数量和功能的下调表明Ts缺陷参与了ITP的发病。此外，ICOS表达降低以及调节抗原呈递细胞上共刺激分子表达能力的丧失，部分解释了Ts介导的抑制功能缺陷。
