IMPAIRED NATURAL-KILLER CYTOTOXICITY IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN GRAVES-DISEASE

We studied the natural killer (NK) activity of peripheral blood mononu clear cells (PBMC) in patients with Graves' disease (GD). Peripheral b lood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 +/- 15.9%), while in 32 euthyroid patients under antithyr oid drug therapy, NK activity was similar to that of controls (46.9 +/ - 17.3 and 49.9 +/- 20.2%, respectively). Furthermore, normalization o f thyroid function with antithyroid drugs was associated with a signif icant increase and normalization of NK activity during the follow-up o f nine GD patients (from 29.2 +/- 17.9 to 48.1 +/- 16.5%). This phenom enon could not be ascribed to a defective number of NK cells because t he amounts of CD56+ and CD16+ cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activ ity of PBMC from patients with toxic multinodular goiter was similar t o that of normal controls (45 +/- 12.8 to 49.9 +/- 20%). No correlatio n was found between natural killer activity and serum levels of free t hyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thry oglobulin and thyroidal microsomal antigen, dose or duration of antith yroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abno rmalities were not associated with a defective IL-2 production by T ce lls, nor with a decreased IL-2R expression. We conclude that in untrea ted Graves' disease there is a decrease in NK cell activity in PBMC, p robably dependent on the autoimmune process. Possible biological and c linical implications are discussed.