Molecular biological study on the pathogenesis of thyroid-associated ophthalmopathy

甲状腺相关眼病发病机制的分子生物学研究

• 批准号: 08671194
• 负责人: HIROMATSU Yuji
• 金额: $ 1.28万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671194/
• 关键词: Graves'ophthalmopathy; Thyroid-associate ophthalmopathy; Apoptosis; T cell clone

In is gnerally accepted that thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder, which is closely associated with Graves'disease. However, the nature of autoantigen and its pathological mechanisms has not been clear. In the present study we have attempted (1) to investigate a role of apoptosis in the enlarged eye muscle tissues on the pathogenesis of TAO and (2) to establish and analyze T cell clones from infiltration lymphocytes in orbital tissues from patients with TAO.We have investigated 20 eye muscle tissues from 20 patients with TAO.Apoptosis was detected in eye muscle cells and the interstitial cells. The percentages of apoptotic nuclei were significantly greater than those in control eye muscle and significantly correlated with the degree of eye muscle enlargement assessed by computed tomography (r=0.47, P<0.05). Fas ws expressed on the surface of eye muscle cells. Fas ligand is expressed in the infiltrating lymphocytes. Those results suggest the involvement of apoptosis on the pathogenesis of TAO.We established 101 T cell clones (TCC), using direct cloning technique, and 3 T cell lines (TCL) from infiltrating T cells in the orbit from patients with TAO.84 TCC were CD4+and 17 were CD8+. Most of TCC showed Th1 pattern of cytokine production or Th0 pattern, suggesting the involvement of Th1 type CD4+T cells in the pathogenesis of TAO.Regarding to the antigen response, none of these TCC did recognize autologous cultured orbital fibroblasts. Autoantigen (s) in TAO are still unknown.

甲状腺相关眼病（TAO）是一种自身免疫性疾病，与Graves病密切相关。然而，自身抗原的性质及其病理机制尚不清楚。本研究通过对20例TAO患者的20例眼肌组织进行细胞凋亡检测，发现TAO患者的眼肌细胞和间质细胞均存在凋亡，并对TAO患者的T细胞克隆进行了分析。凋亡细胞核的百分比显著高于对照眼肌，并与CT评估的眼肌肥大程度显著相关（r=0.47，P<0.05）。Fas在眼肌细胞表面表达。Fas配体在浸润淋巴细胞中表达。采用直接克隆技术从TAO患者眼眶浸润T细胞中分离出101个T细胞克隆（TCC）和3个T细胞系（TCL），其中84个TCC为CD4+，17个为CD8+。多数TCC呈Th1型或Th0型，提示Th1型CD4+T细胞参与了TAO的发病过程。TAO中的自身抗原仍未知。

项目成果

Mari Koga, Yuji Hiromatsu, Atsuo Jimi, Yoichi Inoue, Kyohei Nonaka: "POSSIBLE IN VOLVEMENT OF FAS-MEDIATED APOPTOSIS IN EYE MUSCLE TISSUE FROM PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY." Thyroid. (in press).

Mari Koga、Yuji Hiromatsu、Atsuo Jimi、Yoichi Inoue、Kyohei Nonaka：“可能参与甲状腺相关眼病患者眼部肌肉组织中 FAS 介导的细胞凋亡。”

M Koga, et al.: "POSSIBLE INVOLVEMENT OF FAS-MEDIATED APOPTOSIS IN EYE MUSCLE TISSUE FROM PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY." Thyroid. (in press).

M Koga 等人：“甲状腺相关眼病患者的眼部肌肉组织可能涉及 FAS 介导的细胞凋亡。”

M Koga,et al.: "POSSIBLE INVOLVEMENT OF FAS-MEDIATED APOPTOSIS IN EYE MUSCLE TISSUE FROM PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY." Thyroid. (in press).

M Koga 等人：“甲状腺相关眼病患者的眼部肌肉组织可能涉及 FAS 介导的细胞凋亡。”