Patterns of cellular immune responses to thyrocyte membrane antigens and specific immunoregulatory defects in autoimmune thyroid disease

Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response