van Blokland S C, van Helden-Meeuwsen C G, Wierenga-Wolf A F, Drexhage H A, Hooijkaas H, van de Merwe J P, Versnel M A
Department of Immunology, Erasmus University Rotterdam and University Hospital Rotterdam-Dijzigt, The Netherlands.
Lab Invest. 2000 Apr;80(4):575-85. doi: 10.1038/labinvest.3780062.
Sjögren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjögren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/Ipr mouse, can be used as models for Sjögren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/Ipr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/Ipr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/Ipr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjögren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients.
干燥综合征是一种主要影响唾液腺和泪腺的自身免疫性疾病。在这些腺体中，会出现局灶性淋巴细胞浸润。关于这种自身免疫性疾病的发病机制知之甚少。抗原呈递细胞（APC），如树突状细胞（DC），可能在自身免疫的发病过程中起作用。迄今为止，尚无关于干燥综合征中DC存在情况的数据。几种小鼠品系，如非肥胖糖尿病（NOD）小鼠和MRL/Ipr小鼠，可作为干燥综合征的模型。我们比较了NOD小鼠和MRL/Ipr小鼠下颌下腺（SMG）中涎腺炎的发展情况，特别关注APC的存在。通过免疫组织化学研究了SMG中的DC、巨噬细胞、T细胞和B细胞，然后对阳性染色细胞进行定量。使用NOD-严重联合免疫缺陷（SCID）小鼠研究在无淋巴细胞情况下SMG中APC的存在。在淋巴细胞浸润之前，与对照小鼠和MRL/Ipr小鼠相比，NOD小鼠的SMG中检测到DC数量增加，这表明DC在NOD小鼠涎腺炎的发病中起作用。在NOD小鼠的SMG中，淋巴细胞浸润随时间而组织化。然而，在MRL/Ipr小鼠中，淋巴细胞浸润在出现时就已经组织化了。这种组织化随时间而消失。总之，在两种干燥综合征小鼠模型中描述了两种类型的涎腺炎。在可能导致涎腺炎发展的早期事件以及炎性浸润的组成和组织方面存在差异。人类中也可能存在不同类型的涎腺炎，并且自身免疫反应早期和晚期的发病过程在患者之间也有所不同。
