T-CELL RESPONSES TO ORBITAL ANTIGENS IN THYROID-ASSOCIATED OPHTHALMOPATHY

Thyroid-associated ophthalmopathy (TAO) is most likely to be a T cell- mediated disease, in which cytokines released in the extraocular muscl es activate fibroblasts, increasing glycosaminoglycan production. The nature of the orbital antigen recognized by the infiltrating T cells i s unclear, although it is possible that there is cross-reactivity betw een this and a thyroid autoantigen to explain the close association wi th thyroid autoimmunity. We have tested the ability of human and porci ne eye muscle antigen preparations to stimulate proliferation of circu lating T cells from healthy subjects and patients with TAO or Graves' disease without clinical TAO. Occasional responses were seen, particul arly after depletion of CD8(+) T cells, and two out of 10 TAO patients responded to eye muscle proteins of 25-50 kD after fractionation of a ntigens on gels and subsequent elution. There was no disease-specific response of T cells to R1, R14, D1 and 1D3, recombinant proteins ident ified from screening an eye muscle cDNA library with sera from patient s with autoimmune thyroid disease. We have also found that interferon- gamma (IFN-gamma) production by T cells from TAO patients was not stim ulated by eye muscle membrane antigens or by 1D3. These results sugges t that the frequency of circulating T cells responding to eye muscle a ntigens in TAO is low, and that several candidate orbital antigens, in cluding the 64-kD protein 1D3, are unlikely to be important T cell aut oantigens in this condition.