Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada;
Department of Chemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3X7, Canada; and.
J Immunol. 2014 Jul 1;193(1):96-101. doi: 10.4049/jimmunol.1400561. Epub 2014 May 30.
Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.
碘的摄入增加已知会加速自发性自身免疫性甲状腺炎（碘加速自发性自身免疫性甲状腺炎（ISAT））在 NOD.H2（h4）小鼠中的发生和严重程度。CD4+细胞是 ISAT 发展和维持所必需的，但它们的靶抗原表位仍不清楚。在这项研究中，我们表明，先前鉴定的甲状腺球蛋白（Tg）T 细胞表位 p2549-2560 含有甲状腺素在位置 2553（T4p2553）在 NOD.H2（h4）小鼠中也会引起甲状腺炎以及强烈的特异性 T 和 B 细胞反应。在 ISAT 中，在碘丰富饮食的小鼠中，仅在疾病发作前在甲状腺引流颈淋巴结中检测到针对 T4p2553 的活化 CD4+T 细胞，而在年龄匹配的对照组中则未检测到。此外，在颈淋巴结细胞和甲状腺内淋巴细胞中观察到 CD4+IFN-γ+T4p2553 特异性细胞的选择性富集。从碘喂养或对照小鼠的颈淋巴结细胞中获得的树突状细胞中同样可以检测到 T4p2553，这表明富含碘的饮食有助于自身反应性细胞的激活，而不是自身抗原表位的产生。此外，在强烈的 Tg 特异性自身抗体反应中未检测到自发的 T4p2553 特异性 IgG。据我们所知，这些数据首次确定 Tg T 细胞表位为 ISAT 的自发性靶标。
