Immune reactions in patients with Graves' disease

Abstract

Although Graves' disease exhibits many features of an autoimmune disturbance there is uncertainty regarding, in particular, the role of cell-mediated immunity. Therefore, we undertook a sequential study of peripheral lymphocyte responsiveness to phytomitogens, concentrations and ratios of T and B lymphocytes, and skin hypersensitivity to multiple antigens, throughout periods of antithyroid drug therapy in patients with hyperthyroidism of Graves' disease. Careful attention was paid to obtaining control lymphocyte data with blood from normal subjects matched for age and sex. A micromethod using whole blood was applied to measurement of peripheral lymphocyte responses (incorporation of tritiated [ 3H] thymidine) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM). Total lymphocyte concentrations and the proportions of T and B cells were normal in 26 patients studied; there was a mild excess of total lymphocytes and T cells in 12 patients with fresh disease versus that in six patients with persisting or recurrent hyperthyroidism. Responses of lymphocytes to pokeweed mitogen were normal but to phytohemagglutinin, significant differences from controls were identified: With one day of culture, cells from the patients were more responsive; with six days of incubation, they were less responsive than were cells from corresponding control subjects. These differences were not found with patients restudied after three to 10 months of treatment with propylthiouracil. The ratio of T:B cells varied with the donor's age, as did responses to pokeweed mitogen. Responses to phytohemagglutinin after one and six days of incubation, and to pokeweed mitogen after three days correlated positively with the concentration of serum thyroxine. Delayed hypersensitivity to four antigens injected intradermally was normal; the degree of skin response to tuberculin purified protein derivative correlated significantly with in vitro lymphocyte responses to that antigen. Our data confirm some abnormalities of lymphocyte function in Graves' disease. It remains unclear to what degree reversion to normal during therapy reflects a change in basic pathogenetic mechanisms or an influence of thyroid hormones per se. The importance of age and sex in studies of this nature is emphasized.