Department of Dermatology, Ajou University School of Medicine, Suwon, Yeongtong-Gu, Suwon 443-721, Korea.
Br J Dermatol. 2011 Jun;164(6):1285-91. doi: 10.1111/j.1365-2133.2011.10274.x. Epub 2011 May 17.
The reduced expression of molecules limiting excessive immune responses has been considered a pathogenic mechanism associated with autoimmune diseases.
To understand the implications of costimulatory molecules in Behçet's disease (BD), the expression of CTLA-4 and PD-1 on T-cell subsets and of their ligands CD80, CD86 and PD-L1 on antigen-presenting cells (APCs) was investigated.
Peripheral blood mononuclear cells (PBMC) from 11 patients with active BD, eight patients with inactive BD, eight patients with recurrent aphthous ulcers and 10 healthy volunteers as healthy controls (HC) were stimulated with phorbol myristate acetate and ionomycin. The expression of costimulatory molecules was then analysed by flow cytometry. Soluble CTLA-4 (sCTLA-4) concentrations were determined by enzyme-linked immunosorbent assay and the transcript level of PD-L1 was measured by real-time polymerase chain reaction. The PD-L1 expression in skin lesions of patients with BD was evaluated by immunohistochemistry.
Compared with the HC group, reduced expression of CTLA-4 in CD4+ T cells after stimulation was observed in the active BD group, with no difference in the production of sCTLA-4. CD86 expression, in the resting APCs, was reduced in the active BD group compared with the HC group. PD-L1 expression in the APCs was decreased in the active BD group with or without stimulation of cells. Concordantly, the mRNA levels of PD-L1 in PBMC, and PD-L1 expression in the cutaneous lesions, were low in the active BD group.
The results of this study suggest that altered expression of PD-L1, CTLA-4 and CD86 may be involved in the pathogenesis of BD.
分子表达受限，限制过度免疫反应，被认为与自身免疫性疾病的发病机制有关。
为了了解共刺激分子在贝赫切特病（BD）中的意义，我们研究了 CTLA-4 和 PD-1 在 T 细胞亚群上的表达，以及其配体 CD80、CD86 和 PD-L1 在抗原呈递细胞（APC）上的表达。
采集 11 例活动期 BD 患者、8 例缓解期 BD 患者、8 例复发性口腔溃疡患者和 10 例健康志愿者的外周血单个核细胞（PBMC），用佛波醇肉豆蔻酸酯和离子霉素刺激，然后用流式细胞术分析共刺激分子的表达。通过酶联免疫吸附试验测定可溶性 CTLA-4（sCTLA-4）浓度，通过实时聚合酶链反应测定 PD-L1 的转录水平。通过免疫组化评估 BD 患者皮肤病变中的 PD-L1 表达。
与健康对照组相比，活动期 BD 组刺激后 CD4+T 细胞中 CTLA-4 的表达减少，但 sCTLA-4 的产生没有差异。与健康对照组相比，活动期 BD 组静止 APC 中 CD86 的表达减少。刺激或不刺激细胞时，APC 中 PD-L1 的表达在活动期 BD 组中均降低。相应地，PBMC 中 PD-L1 的 mRNA 水平以及 BD 组皮肤病变中的 PD-L1 表达均较低。
本研究结果提示，PD-L1、CTLA-4 和 CD86 的表达改变可能与 BD 的发病机制有关。
