Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease.
Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D008713:Methimazole / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology
D001323:Autoantibodies; D006684:HLA-DR Antigens; D011989:Receptors, Thyrotropin; D008713:Methimazole