Cytotoxic mechanisms in autoimmune thyroid disorders and thyroid-associated ophthalmopathy

Cytotoxic antibodies against thyroid cells and eye muscle cells, measured as antibody-dependent complement-mediated cytotoxicity and ADCC, have been demonstrated in sera from patients with Hashimoto's thyroiditis and thyroid-associated ophthalmopathy, respectively. Such antibodies are probably never present in the absence of target cell damage. Because cell-mediated cytotoxicity plays an important role in experimental autoimmune thyroiditis, further studies are necessary to elucidate the roles of NK cells, K cells, and cytotoxic T lymphocytes in the thyroid cell damage in AITD and orbital cell damage in ophthalmopathy. The socalled aberrant expression of HLA-DR antigens on thyroid cells and orbital cells and the gamma-interferon production by activated T cells may be both intimately associated with the development of autoimmune reactions in the thyroid and the orbit. Cytotoxic antibodies and cytotoxic T lymphocytes against antigens shared between eye muscle cells and thyroid cells may be directly responsible for the eye muscle cell damage in endocrine ophthalmopathy, and they may explain the close association of ophthalmopathy with Graves' hyperthyroidism and Hashimoto's thyroiditis.