Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Thromb Haemost. 2019 May;119(5):758-765. doi: 10.1055/s-0039-1679909. Epub 2019 Feb 26.
The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells turns off autoreactive T cells and induces peripheral tolerance. Aberrant PD-1/PD-L signalling could result in a breakdown of peripheral tolerance and lead to autoimmune diseases. In this study, we detected PD-1 and PD-L expression on T cells and dendritic cells (DCs) in immune thrombocytopenia (ITP) patients with active disease by flow cytometry. The effects of PD-L1-Fc fusion protein (PD-L1-Fc) on T cells and on secretion of interferon-γ (IFN-γ) and interleukin-2 (IL-2) were detected by flow cytometry and enzyme-linked immunosorbent assay, respectively. Compared with healthy controls, PD-1 expression was significantly increased in CD4 T cells and CD8 T cells from patients with active ITP. However, PD-L1 expression on monocyte-derived DCs was lower in patients with active ITP than in healthy controls. In vitro assays revealed that PD-L1-Fc increased T cell apoptosis, inhibited activation and proliferation of CD4 T cells and CD8 T cells and decreased IFN-γ and IL-2 secretion in patients with active ITP. These results suggest that the aberrant PD-1/PD-L negative co-stimulatory pathway may play a role in ITP. Enhancing PD-1/PD-L signalling might be a promising therapeutic approach for ITP patients by enhancing T cell apoptosis, inhibiting T cell activation and proliferation and reducing secretion of inflammatory factors.
程序性死亡受体 1（PD-1）与其配体 PD-L1 和 PD-L2 在抗原呈递细胞上的结合会关闭自身反应性 T 细胞并诱导外周耐受。异常的 PD-1/PD-L 信号可能导致外周耐受的破坏，并导致自身免疫性疾病。在这项研究中，我们通过流式细胞术检测了处于活动期的免疫性血小板减少症（ITP）患者 T 细胞和树突状细胞（DC）上的 PD-1 和 PD-L 表达。通过流式细胞术和酶联免疫吸附试验分别检测了 PD-L1-Fc 融合蛋白（PD-L1-Fc）对 T 细胞以及干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）分泌的影响。与健康对照组相比，处于活动期的 ITP 患者的 CD4 T 细胞和 CD8 T 细胞中 PD-1 表达显著增加。然而，与健康对照组相比，处于活动期的 ITP 患者的单核细胞衍生的 DC 上的 PD-L1 表达较低。体外试验表明，PD-L1-Fc 增加了 T 细胞凋亡，抑制了处于活动期的 ITP 患者的 CD4 T 细胞和 CD8 T 细胞的活化和增殖，并减少了 IFN-γ和 IL-2 的分泌。这些结果表明，异常的 PD-1/PD-L 负共刺激途径可能在 ITP 中起作用。通过增强 T 细胞凋亡、抑制 T 细胞活化和增殖以及减少炎症因子的分泌，增强 PD-1/PD-L 信号可能是 ITP 患者有前途的治疗方法。
