Methimazole therapy in Graves' disease influences the abnormal expression of CD69 (early activation antigen) on T cells

At present, the in vivo response of T, B and natural killer (NK) cells to antithyroid drug therapy remains largely unknown. In the present study, we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating T and NK cell subsets, some of them expressing cell surface activation antigens involved in the very early phase of the immune response, in a group of 17 hyperthyroid, untreated patients with Graves' disease (GD). As one of the first events during T cell activation is the expression of interleukin (IL) receptors, we also studied the binding of IL-2 and IL-6 to T cells. Patients with Graves' disease were sequentially studied at diagnosis/before treatment (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age-and sex-matched control volunteers and a group of 20 untreated/euthyroid patients with Graves' disease in long-term remission. The combination of flow cytometry and three-color immunofluorescence revealed a clear (P<0.01) decrease in the percentage of NK cells before and during the whole course of therapy with respect to both controls and patients with Graves' disease who were in long-term remission. Before therapy, a marked increase (P<0.001) in the ratio of B to NK cells was also observed, thereafter, a slight decrease in this ratio was observed, although normal values were detected only in patients in long-term remission. Expression of the CD69 early activation antigen in the hyperthyroid untreated patients with Graves' disease was clearly increased (P<0.01) with respect to both controls and patients with Graves' disease who were in long-term remission. This abnormal CD69 expression was found to be significantly reduced (P<0.001) by methimazole therapy, and this represents a new effect of the drug. Expression of the low-affinity receptor for IL-2 (CD25) - another early T cell activation marker - was not altered in Graves' disease, but the binding of IL-2 and IL-6 to T cells exhibited a progressive and parallel increase during the first 30 days of therapy, decreasing thereafter. Our results show that methimazole therapy downregulates the abnormally high expression of the CD69 early activation antigen on T cells, being less effective on inducing changes in other T cell activation markers and in NK cells.