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BACKGROUND: Patients with autoimmune thyroid diseases, including Graves' disease and Hashimoto's disease, have marked lymphocytic infiltration in their thyroid glands. We examined the gene for the variable regions of the alpha-chain of the human T-cell receptor (the V alpha gene) in intrathyroidal T cells to determine whether the infiltration is a secondary heterogeneous immune response or a more restricted, and therefore primary and presumably pathogenetic, reaction to thyroid autoantigens. METHODS: We used the polymerase chain reaction to detect small numbers of T cells expressing the variable region of the V alpha gene. Different oligonucleotides were used to amplify complementary DNA for the 18 known families of the V alpha gene in intrathyroidal T cells from 9 patients with autoimmune thyroid disease. We compared the findings with the results in patients with nonautoimmune thyroid disease as well as those in normal subjects. RESULTS: We found marked restriction in the expression of T-cell-receptor V alpha genes by T cells from the thyroid tissue of patients with autoimmune thyroid disease. An average of only 5 of the 18 V alpha genes were expressed in such samples, as compared with 17 V alpha genes expressed in peripheral-blood T cells from the same patients. No such restriction was found in thyroid tissue from patients with nonautoimmune thyroid disease. The predominantly expressed V alpha genes differed from patient to patient, however, with no clear association with the type of disease. CONCLUSIONS: Intrathyroidal T-cell accumulation in autoimmune thyroid disease is highly restricted and points to the primacy of T cells in causing thyroid disorders. These results present the possibility of using antibodies to the T-cell receptor for the specific inhibition of abnormal T-cell function in autoimmune thyroid disease.
Davies et al. (Thu,) studied this question.