Molecular biological study on the pathogenesis of thyroid-associated ophthalmopathy

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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.