SPECIFIC SUPPRESSOR T CELL FUNCTION IN A PATIENT WITH GRAVES' DISEASE AND HER HEALTHY IDENTICAL TWIN

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Abstract
Immunoregulatory defects have been suggested in autoimmune disorders including Graves'' disease. The finding that Concanavalin A-induced suppressor T cell function was sub-optimal in Graves'' disease has been disputed; a restricted defect in TSH-receptor antigen-specific suppressor cells has been proposed. Both specific and non-specific suppressor cell function were studied in a pair of HLA identical twins, 1 of whom had Graves'' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/106 cells) the patient''s mononuclear cells (MNC) incorporated more {3H}-thymidine (7365 cpm/106 cells) in response to thyroid membrane antigen (TMA). Removal of glass-adherent cells before addition of antigen increased {3H} uptake by cells from the healthy twin to 1808 cpm but reduced those from the Graves'' twin to 3411 cpm. The influence of MNC cultured with Con A or TMA for 24 h upon {3H}-thymidine uptake by 2 .times. 106 indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non-specific and specific suppressor cell function, respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNC from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient''s MNC triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNC and TMA, less blast transformation was found compared to an equal number of fresh cells (3H-thymidine uptake 3250 vs. 7365 cpm/106). Preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/106 cells). The HLA identical healthy twin apparently has TMA autoreactive lymphocytes regulated by adherent regulatory cells. The increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of {3H} incorporation upon their removal. In the patient, the specific suppressor cell defect is more severe than the non-specific defect. Lack of specific TMA-induced triggering may be the critical immunoregulatory defect in Graves'' disease.