Molecular biological study on the pathogenesis of thyroid-associated ophthalmopathy

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。在本研究中，我们试图(1)探讨扩大的眼肌组织中的细胞凋亡在TAO发病机制中的作用；(2)建立和分析TAO患者眼眶组织中浸润性淋巴细胞的T细胞克隆。细胞凋亡率明显高于对照眼肌，且与CT眼肌增大程度显著相关(r=0.47，P&lt；0.05)。Fas-ws表达于眼肌细胞表面。Fas配体在浸润性淋巴细胞中表达。我们用直接克隆技术建立了101个T细胞克隆(TCC)，从TAO患者眼眶内浸润性T细胞中分离出3个T细胞系(TCL)，其中84个TCC为CD4+，17个为CD8+。大多数TCC表现为Th1型细胞因子产生或Th0模式，提示Th1型CD4+T细胞参与了TAO的发病。就抗原反应而言，这些TCC均不识别自体培养的眼眶成纤维细胞。TAO患者的自身抗原(S)尚不清楚。

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.