Study on the pathogenesis of thyroid-associated ophthalmopathy

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lt is generally 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 cytokine profile of the enlarged eye muscle tissues and retrobulbar fat tissues from patients with TAO. (2) We also investigated T cell receptor Vβ gene usage in these 2 sites of the lesions whether T cells recognize the same autoantigen or not.We have studied 14 eye muscle tissues and 29 orbital fat tissues from 33 patients with TAO. Cytokine gene expression was assessed by RT-PCR. Th1 and proinflammatory cytokines were predominantly detected in eye muscle tissues, while Th2 cytokines were predominantly detected in orbital fat tissues. Eye muscle enlargement, assessed by CT, was significantly correlated with TNFα gene expression in eye muscle. On the other hand, orbital fat volume was negatively correlated with IL-4 and IL-10 gene expression. These results suggest that both Th1 like and Th2 like immune reactions may play role in the development of two components of ophthalmopathy.We have investigated the T cell clonality in 3 extraocular muscle tissues and 5 retrobulbar fat tissues from patients with TAO. T cell receptor Vβ gene usage was assessed by RT-PCR and SSCP methods. Several bands were detected in each Vβ gene, suggesting the existence of T cell clonality in these tissues. Furthermore, there were several distinct bands at the same mobility between eye muscle and orbital fat tissues. The present study suggest that both T cells reactive with the same autoantigen between 2 sites (eye muscle tissue and orbital fat tissue) and T cells reactive with the other antigens, are accumulating in those 2 sites in TAO. T cell immunity may be important in the development of ophthalmopathy.