Li Yu-Shu, Kanamoto Naotetsu, Hataya Yuji, Moriyama Kenji, Hiratani Hitomi, Nakao Kazuwa, Akamizu Takashi
Translational Research Center, Kyoto University School of Medicine, 54 Shogoin Kawaharacho Sakyo-ku, Kyoto 606-8507, Japan.
Endocrinology. 2004 May;145(5):2524-30. doi: 10.1210/en.2003-1654. Epub 2004 Feb 5.
The expression of major histocompatibility complex (MHC) class II molecules on thyrocytes has been demonstrated in autoimmune thyroid diseases. However, the role of this aberrant MHC class II in disease development is controversial. In particular, it remains unknown whether MHC class II expression on thyrocytes, which are nonprofessional antigenpresenting cells, plays a role in inducing autoimmune processes. To clarify this issue, we have produced transgenic mice harboring an MHC class II gene ligated to the promoter of the rat TSH receptor. We obtained three lines of transgenic mice, and the expression of MHC class II by the thyrocytes was demonstrated by immunofluorescence staining and flow cytometry. Our examination revealed no obvious abnormalities in thyroid histology or in thyroid autoantibody production in these transgenic mice. Although serum-free T(4) levels were slightly lower than those of their nontransgenic littermates, no transgenic mouse suffered from clinical hypothyroidism or hyperthyroidism. Furthermore, thyroid lymphocytic infiltration was absent, and MHC class II-expressing thyrocytes obtained from transgenic mice failed to stimulate the proliferation of autologous T cells in vitro. Taken together, these results show that transgenic mice with MHC class II molecules on their thyrocytes do not develop apparent autoimmune thyroid diseases, suggesting that aberrant MHC class II expression alone is not sufficient to induce thyroid autoimmunity.
在自身免疫性甲状腺疾病中,已证实甲状腺细胞上主要组织相容性复合体(MHC)II类分子的表达。然而,这种异常的MHC II类分子在疾病发展中的作用存在争议。特别是,甲状腺细胞作为非专职抗原呈递细胞,其MHC II类分子的表达是否在诱导自身免疫过程中发挥作用仍不清楚。为了阐明这个问题,我们构建了携带与大鼠促甲状腺激素受体启动子相连的MHC II类基因的转基因小鼠。我们获得了三系转基因小鼠,并通过免疫荧光染色和流式细胞术证实了甲状腺细胞中MHC II类分子的表达。我们的检查发现这些转基因小鼠的甲状腺组织学或甲状腺自身抗体产生没有明显异常。尽管血清游离T4水平略低于其非转基因同窝小鼠,但没有转基因小鼠患有临床甲状腺功能减退或甲状腺功能亢进。此外,没有甲状腺淋巴细胞浸润,从转基因小鼠获得的表达MHC II类分子的甲状腺细胞在体外未能刺激自体T细胞的增殖。综上所述,这些结果表明,甲状腺细胞上表达MHC II类分子的转基因小鼠不会发生明显的自身免疫性甲状腺疾病,这表明单独的异常MHC II类分子表达不足以诱导甲状腺自身免疫。