Tang H, Chen K, Wei Y, Sharp G C, McKee L, Braley-Mullen H
Departments of Internal Medicine, Molecular Microbiology & Immunology and Pathology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Int Immunol. 2000 Dec;12(12):1629-39. doi: 10.1093/intimm/12.12.1629.
Experimental autoimmune thyroiditis (EAT) with granulomatous histopathology (G-EAT) can be induced by cells from mouse thyroglobulin (MTg)-immunized donors activated in vitro with MTg and IL-12. G-EAT lesions reach maximum severity 18-21 days after cell transfer and, if some thyroid follicles remain, lesions almost completely resolve by day 35. CD8(+) cells are required for G-EAT resolution. To begin to determine the mechanisms involved in G-EAT resolution, apoptosis in thyroids was analyzed by TUNEL staining. Apoptotic thyrocytes and inflammatory cells were present in the thyroids of both CD8(+) and CD8-depleted recipient mice at day 19-21. By day 35, apoptotic cells were rare in thyroids of mice whose lesions had resolved; the few apoptotic inflammatory cells were generally in close proximity to thyroid follicles. Thyroids of CD8-depleted mice had ongoing inflammation at day 35 and most apoptotic cells were thyroid follicular cells. The expression of Fas and Fas ligand (FasL) mRNA in thyroids was also determined by RT-PCR in both CD8(+) and CD8-depleted recipient mice. Fas was expressed in normal thyroids and its expression was relatively constant throughout the course of disease. FasL mRNA was not expressed in normal thyroids. FasL mRNA expression generally correlated with G-EAT severity, being maximal at day 21 and diminishing as lesions resolved. However, FasL mRNA expression in thyroids of CD8-depleted mice in which resolution was delayed was decreased compared to thyroids of CD8(+) mice with comparable disease severity, suggesting that FasL expressed by CD8(+) cells may play a role in G-EAT resolution.
具有肉芽肿组织病理学特征的实验性自身免疫性甲状腺炎（G-EAT）可由来自用小鼠甲状腺球蛋白（MTg）免疫的供体的细胞在体外与MTg和IL-12共同激活后诱导产生。G-EAT损伤在细胞转移后18-21天达到最大严重程度，如果仍有一些甲状腺滤泡残留，损伤在第35天时几乎完全消退。G-EAT的消退需要CD8(+)细胞。为了开始确定G-EAT消退所涉及的机制，通过TUNEL染色分析甲状腺中的细胞凋亡情况。在第19-21天，CD8(+)和CD8缺失的受体小鼠的甲状腺中均存在凋亡的甲状腺细胞和炎性细胞。到第35天时，损伤已消退的小鼠甲状腺中凋亡细胞很少见；少数凋亡的炎性细胞通常靠近甲状腺滤泡。CD8缺失小鼠的甲状腺在第35天时仍有持续炎症，且大多数凋亡细胞是甲状腺滤泡细胞。还通过RT-PCR在CD8(+)和CD8缺失的受体小鼠中测定了甲状腺中Fas和Fas配体（FasL）mRNA的表达。Fas在正常甲状腺中表达，且在疾病过程中其表达相对恒定。FasL mRNA在正常甲状腺中不表达。FasL mRNA表达通常与G-EAT严重程度相关，在第21天达到最大值，随着损伤消退而减少。然而，与具有相当疾病严重程度的CD8(+)小鼠的甲状腺相比，CD8缺失小鼠甲状腺中FasL mRNA表达在消退延迟时降低，这表明CD8(+)细胞表达的FasL可能在G-EAT消退中起作用。
