title: Specific suppressor T cell function in a patient with Graves' disease and her healthy identical twin.
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 instead been proposed by Okita et al. (1980). To explore this further, we studied both specific and non-specific suppressor cell function in a pair of HLA identical twins, one of whom had Graves' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/10(6) cells) the patient's mononuclear cells (MNCs) incorporated more (3H)-thymidine (7365 cpm/10(6) 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 MNCs cultured with Con A or TMA for 24 h upon (3H)-thymidine uptake by 2 X 10(6) 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 MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H-thymidine uptake 3250 vs 7365 cpm/10(6). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/10(6) cells). We conclude that (1) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) 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; (3) in the patient, the specific suppressor cell defect is more severe than the non-specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory defect in Graves' disease.
mesh_terms: D000328:Adult; D000954:Antigens, Surface; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D004200:Diseases in Twins; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology*; D014430:Twins, Monozygotic
chemical_list: D000954:Antigens, Surface; D003208:Concanavalin A; D013936:Thymidine