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Studies of HLA-DR Expression on Cultured Human Thyrocytes: Effect of Antithyroid Drugs and Other Agents on Interferon--Induced HLA-DR Expression^*

JAIME AGUAYO, MAKOTO IITAKA, VAS V. ROW and ROBERT VOLPÉ

Endocrinology Research Laboratory, Department of Medicine, The Wellesley Hospital, University of Toronto Toronto, Ontario, Canada

Address requests for reprints to: Dr. Robert Volpé, The Wellesley Hospital, 160 Wellesley Street East, Toronto, Ontario, M4Y 1J3 Canada.

There have been conflicting reports on whether antithyroid drugs (ATD) act as immunosuppressive agents in patients with autoimmune thyroid disease. While some have claimed that methimazole (MMI) affects the immune system directly, we and others have suggested that its apparent immunosuppressive activity is due to its ability to inhibit thyrocyte, rather than immunocyte, activity. To further address the question, we studied the action of ATD on interferon- (IFN)-induced HLA-DR expression on thyrocytes in tissue culture. We used a cytotoxicity assay, using chromium-51-labeled Graves’ disease (GD) thyrocytes and normal thyrocytes incubated sequentially with a monoclonal antibody against HLA-DR and complement, with a cytotoxicity index as the measure of thyrocyte HLA-DR expression. MMI and propylthiouracil (PTU) were added along with 200 U/mL IFN to thyrocytes cultured for 10–14 days. IFN or supernatants from leukoagglutininstimulated peripheral blood mononuclear cells (PBMC) stimulated thyrocyte HLA-DR expression; however, the addition of MMI or PTU to either the PBMC or thyrocytes caused no inhibition of the IFN or PBMC IFN stimulation of thyrocyte HLA-DR expression, using either normal or GD thyrocytes. Potassium perchlorate and sodium iodide also had no effect on IFN-induced thyrocyte HLA-DR expression. TSH (either bovine or human) did not induce HLA-DR expression on thyrocytes by itself, but did enhance IFN-induced HLA-DR expression in normal, but not GD, thyrocytes; once again, the further addition of MMI or PTU did not inhibit the enhancing effect of TSH on thyrocyte HLA-DR expression. Low concentrations of TSH binding inhibitory immunoglobulin (TBII; 100 µg/mL) did not alter the cytotoxicity index, but at 400 µg/mL or more it enhanced HLA-DR expression on normal, but not GD, thyrocytes in a manner similar to TSH; like TSH, it did not induce thyrocyte HLA-DR expression by itself. Moreover, addition of MMI to the combination of IFN and TBII did not inhibit the response of thyrocytes in terms of HLA-DR expression.

We conclude that ATD do not alter thyrocyte HLA-DR expression in vitro; however, the ATD may still cause immune effects in vivo secondary to their influence on thyroid hormone formation or synthesis or by inhibition of thyroid antigen presentation, which indirectly may result in an immunomodulatory effect. While TSH and TBII similarly enhanced the IFN-induced expression of HLA-DR on normal thyrocytes, they did not do so in GD thyrocytes. There was no significant difference between GD and normal thyrocytes in terms of response to IFN or ATD; however, the lack of further enhancement of IFN--induced HLA-DR expression in GD thyrocytes by TSH or TBII may represent a form of down-regulation of these cells.

^* This work was supported by a grant (MT-859) from the Medical Research Council of Canada. Presented in part at the 69th Annual Meeting of the Endocrine Society, Indianapolis, IN, June 10–13, 1987.

Fellow of the Angus Foundation, The Wellesley Hospital.

Received August 26, 1987.

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