Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy.
Rheumatology Unit, Clinical Science and Biotechnology Department, University of L'Aquila, Via dell'Ospedale, s.n.c., L'Aquila I-67100, Italy.
J Autoimmun. 2014 Jun;51:38-43. doi: 10.1016/j.jaut.2014.01.030. Epub 2014 Jan 24.
Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters.
Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed.
In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells.
Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease.
越来越多的证据表明，IL-17 产生的 T 细胞缺乏 CD4 和 CD8 分子，被定义为双阴性（DN）细胞，在许多系统性自身免疫性疾病的发病机制中发挥关键作用。我们最近证明，这种 T 细胞亚群在外周血（PB）中扩张原发性干燥综合征（pSS）患者中，产生 IL-17 并在小唾液腺（MSG）中积累。我们旨在研究早期 pSS 中的腺内和 PB DN T 细胞，以验证其与 MSG 组织学模式和临床参数的可能相关性。
通过流式细胞术和免疫荧光染色分别评估 pSS 患者 PB 单个核细胞和 MSG 的配对样本。还进行了组织学分析以确定组织学评分、B/T 细胞分离和生发中心（GC）样结构的存在。
在 pSS 的早期阶段，循环 DN T 细胞似乎尚未扩增，与循环 CD4（+）Th17 细胞呈负相关。浸润性 DN T 细胞的数量与腺体受累程度、GC 样结构的存在和干燥症状相关，与循环 DN T 细胞呈负相关。
我们的发现表明，DN T 细胞积极参与导致 pSS 腺体功能障碍和损伤的致病机制，并可能在疾病发生期间异位淋巴生成发展中发挥作用。
