Konno Akihiro, Takada Kensuke, Saegusa Junzo, Takiguchi Mitsuyoshi
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Autoimmunity. 2003 Jun;36(4):247-54. doi: 10.1080/0891693031000141077.
Subpopulations of infiltrating lymphocytes, professional antigen-presenting cells (APCs), and Th1/Th2 cytokines that could initiate an autoimmune sialodacryoadenitis were studied in the IQI/Jic mouse model of primary Sjögren's syndrome. Although lymphocytic infiltrations were first seen in submandibular glands (SMGs) of females and in lacrimal glands (LGs) of males at 8 weeks of age, clusters of MHC class II+, CD11c+, B7-2+ dendritic cells (DCs) were already localized in these tissues at 4 weeks. At 8 weeks, the infiltrating lymphocytes consisted of almost equal numbers of B cells and CD4+ T cells. In the inflammatory foci, MHC class II+, CD11c+, B7-2+ DCs formed network-like structures. Duct cells in the lesions showed immunoreactivities for MHC class II and ALCAM (a costimulatory adhesion molecule). IL-12 and IFN-gamma transcripts were detected by RT-PCR in SMGs of females and in LGs of males at 8-12 weeks. These results suggest that the clustered DCs might play an important role in the initiation of the adenitis, and further suggest that the DCs and epithelial cells may participate in the activation of CD4+ T cells. It is also likely that Th1 cytokines mediate the functional interactions between the APCs and CD4+ T cells in the early lesions.
在原发性干燥综合征的IQI/Jic小鼠模型中,研究了可能引发自身免疫性涎泪腺炎的浸润淋巴细胞亚群、专职抗原呈递细胞(APC)以及Th1/Th2细胞因子。尽管在8周龄时首次在雌性小鼠的下颌下腺(SMG)和雄性小鼠的泪腺(LG)中观察到淋巴细胞浸润,但在4周龄时,MHC II类、CD11c、B7-2阳性的树突状细胞(DC)簇已定位在这些组织中。在8周龄时,浸润的淋巴细胞由数量几乎相等的B细胞和CD4+ T细胞组成。在炎症灶中,MHC II类、CD11c、B7-2阳性的DC形成网络状结构。病变中的导管细胞对MHC II类和ALCAM(一种共刺激黏附分子)显示免疫反应性。在8至12周龄时,通过RT-PCR在雌性小鼠的SMG和雄性小鼠的LG中检测到IL-12和IFN-γ转录本。这些结果表明,聚集的DC可能在腺炎的起始中起重要作用,进一步表明DC和上皮细胞可能参与CD4+ T细胞的激活。Th1细胞因子也可能在早期病变中介导APC与CD4+ T细胞之间的功能相互作用。