MODULATION OF THE IL-2 PRODUCTION DEFECT IN-VITRO IN GRAVES-DISEASE

IL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including G raves' disease (GD). This production defect in hyperthyroid GD was res tored to normal by antithyroid drug therapy or during remission. Howev er, its underlying mechanism and role in the autoimmune process are st ill uncertain. The present study was undertaken in order to screen the in vitro IL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid ho rmone or antithyroid drugs had no effect on IL-2 production in vitro. Cultures were found to be free of soluble inhibitors of IL-2 productio n or action. IL-1 deficiency as a cause of the IL-2 defect was ruled o ut; rather, Graves' adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E(2) (PG E(2)). The latter was not found to be responsible for the decreased IL -2 production. IL-2 production by Graves' mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or sub stitution with normal adherent cells; (ii) preincubation of mononuclea rs for 24-72 h before mitogen stimulation; (iii) the synergistic actio n of a phorbol ester and a calcium ionophore. These data indicate that inhibition by activated adherent cells accounts for the in vitro IL-2 production defect in GD. This inhibition is not mediated by soluble f actors, but probably through direct interaction with the producing cel ls, and is reversible in rested cultures or through a bypassed signal transduction.