CD40 on salivary gland epithelial cells: high constitutive expression by cultured cells from Sjogren's syndrome patients indicating their intrinsic activation
CD40 on salivary gland epithelial cells: high constitutive expression by cultured cells from Sjogren's syndrome patients indicating their intrinsic activation
复制标题
DOI：
10.1046/j.1365-2249.2002.01752.x
复制
发表时间：
2002-02-01
影响因子：
4.6
通讯作者：
Manoussakis, MN
中科院分区：
文献类型：
--
作者：
Dimitriou, ID;Kapsogeorgou, EK;Manoussakis, MN
CD 40已在造血和非造血细胞的扩展列表中被鉴定，并且基于其在多种细胞介导的应答中的作用及其参与慢性炎性疾病的发病机制的潜力而受到越来越多的关注。干燥综合征（SS）是一种自身免疫性外分泌病，其特征是外分泌腺的慢性淋巴细胞浸润和上皮组织的异常激活。我们研究了CD 40蛋白在培养的非肿瘤性唾液腺上皮细胞（SGEC）系，以及从17 SS患者和12个对照组获得的小SG活检的表达。免疫细胞化学和流式细胞术分析显示，在长期培养的SGEC细胞系的表面上存在组成型表达的CD 40分子，其可进一步由干扰素-γ（IFN-γ）和IL-1 β细胞因子诱导，但不受肿瘤坏死因子-α（TNF-α）、IL-4、IL-6、粒细胞-巨噬细胞集落刺激因子（GM-CSF）或IFN-α诱导。通过CD 40触发SGEC增强粘附分子细胞间粘附分子-1（ICAM-1）/CD 54的表面表达，但不增强MHC I类和II类（HLA-DR）分子的表面表达。与对照组相比，SS患者来源的SGEC细胞系中的自发性CD 40表达显著更高（P < 0.001），这表明它们的内在活化状态。在SG活检中，CD 40由淋巴细胞、导管上皮细胞和内皮细胞组成性表达，但不由其他腺细胞类型，如腺泡细胞、肌上皮细胞和成纤维细胞表达。此外，在SS患者的活检组织中，在30-50%的浸润淋巴细胞中也检测到CD 40 L染色。我们的研究结果表明SGEC的免疫调节潜力，并提供进一步的支持，在SS的唾液上皮细胞的内在激活模型，这些细胞积极参与诱导和维持患者的淋巴细胞浸润。
CD40 has been identified in an expanding list of haematopoietic and non-haematopoietic cells and has received an increased interest based on its role in a variety of cell-mediated responses and its potential to participate in the pathogenesis of chronic inflammatory disorders. Sjogren's syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. We studied the expression of CD40 protein in cultured non-neoplastic salivary gland epithelial cell (SGEC) lines as well as in minor SG biopsies obtained from 17 SS patients and 12 controls. Immunocytochemical and flow cytometric analyses had revealed the occurrence of constitutively expressed CD40 molecules on the surface of long-term cultured SGEC lines, which could be further induced by interferon-gamma (IFN-gamma) and IL-1beta cytokines, but not tumour necrosis factor-alpha (TNF-alpha), IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IFN-alpha. Triggering of SGEC through CD40 enhanced the surface expression of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1)/CD54, but not MHC class I and class II (HLA-DR) molecules. Spontaneous CD40 expression was significantly higher in SGEC lines derived from SS patients, compared with controls (P < 0.001), which is suggestive of their intrinsically activated status. In SG biopsies, CD40 was constitutively expressed by lymphocytes, ductal epithelial cells and endothelial cells but not by other glandular cell types, such as acinar cells, myoepithelial cells and fibroblasts. In addition, CD40L staining was also detected in 30-50% of the infiltrating lymphocytes in the biopsies of SS patients. Our findings indicate the immunoregulatory potential of SGEC and lend further support to a model of intrinsic activation in salivary epithelia in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.