Many M C, Costagliola S, Detrait M, Denef F, Vassart G, Ludgate M C
Department of Histology, Louvain Medical School, and Institut de Recherche en Biologie Humaine et Nucleaire, Universite Libre de Bruxelles, Brussels, Belgium.
J Immunol. 1999 Apr 15;162(8):4966-74.
In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we have examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroiditis with considerable follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in controls. None of the NOD animals developed any orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the receptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose tissue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital changes or thyroiditis were observed in control BALB/c mice. We have induced orbital pathology having many parallels with human TED, only in BALB/c mice, suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for the development of TED.
在先前的研究中，我们已将甲状腺炎转移至用人类促甲状腺激素（TSH）受体（TSHR）致敏的脾细胞处理过的未致敏BALB/c和NOD小鼠。由于TSHR与甲状腺眼病（TED）的发病机制有关，我们已检查了用TSHR融合蛋白或基因免疫法产生的TSHR致敏T细胞受体小鼠的眼眶。在NOD小鼠中，26只接受TSHR致敏T细胞处理的动物中有25只发生了甲状腺炎，伴有相当程度的滤泡破坏、大量活化的CD8+T细胞以及IFN-γ免疫反应性。甲状腺素水平降低。对照组未诱发甲状腺炎。没有一只NOD动物出现任何眼眶病变。35只BALB/c小鼠接受了TSHR致敏的脾细胞。60%-100%的小鼠诱发了甲状腺炎，包括活化的T细胞、B细胞以及IL-4和IL-10免疫反应性。诱导产生了针对该受体的自身抗体，包括TSH结合抑制性免疫球蛋白。25只BALB/c小鼠的眼眶中有17只出现了变化，包括脂肪组织堆积、高碘酸希夫阳性物质引起的水肿、肌纤维解离、TSHR免疫反应性的存在以及淋巴细胞和肥大细胞浸润。对照BALB/c小鼠未观察到眼眶变化或甲状腺炎。我们仅在BALB/c小鼠中诱发了与人类TED有许多相似之处的眼眶病变，这表明对TSHR的Th2自身免疫反应可能是TED发生的先决条件。
