Studies on thyroglobulin-specific suppressor T cell function in autoimmune thyroid disease.
T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.
Mori
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Hamada
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DeGroot
L J
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology; D005260:Female; D006111:Graves Disease / Q000276:immunology; D006462:Hemolytic Plaque Technique; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011970:Receptors, Histamine H2 / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology* / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013954:Thyroglobulin / Q000276:immunology; D013959:Thyroid Diseases / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology
D011970:Receptors, Histamine H2; D013954:Thyroglobulin