Interleukin 2-Activated Killer Cells Do Not Mediate Autologous Thyrocyte Lysis in Autoimmune Thyroid Disease In Vitro

Abstract

Because of interest in IL-2, and IL-2-activated killer cell-induced hypothyroidism in humans, we attempted to study an in vitro system that might prove to illuminate this disorder. We have thus studied interleukin 2 (IL-2—0,12.5, 25, or 50 U/mL) activated killer cell-mediated autologous thyrocyte lysis, as well as cytotoxic activity in IL-2-stimulated mononuclear cell supernatants in 7 patients with autoimmune thyroid disease (2 Graves' disease and 5 Hashimoto's thyroiditis) using the ⁵¹Cr release assay. Controls included 14 patients with nonautoimmune thyroid disease (3 nontoxic goiter, 8 follicular thyroid adenoma, 2 papillary thyroid carcinoma, and 1 medullary carcinoma of the thyroid). Soluble IL-2 receptor (sIL-2R) in supernatants of peripheral mononuclear cells stimulated by IL-2 from these patients also was measured. Whereas in the control preparations, IL-2-activated killer cell activity was increased in a dose-dependent fashion relative to the IL-2 concentration, as well as to the effector cell/target cell ratio, in preparations from patients with autoimmune thyroid disease, this activity was not elevated as the IL-2 concentration was increased. The susceptibility of thyrocytes to the lytic effect of IL-2-activated killer cells was higher in controls than that in autoimmune thyroid disease (at concentrations of IL-2 of 0,12.5, 25, and 50 U/mL) (p < 0.01, respectively). Although the cytotoxic activity in supernatants from IL-2-stimulated mononuclear cells from controls was minimal and much less than that of IL-2-activated killer cell activity (p < 0.001), this value was greater than that from the supernatants from preparations from autoimmune thyroid disease (p < 0.05). On the other hand, sIL-2R in supernatants was increased when IL-2 was added to the mononuclear cell culture medium in preparations from both controls (p < 0.01) and autoimmune thyroid disease (p < 0.05). sIL-2R values in supernatants from controls were not different from those from autoimmune thyroid disease. Thus, T cells from autoimmune thyroid disease normally are activated in response to IL-2. However, the IL-2-activated killer cell activity and cytotoxic activity of IL-2-stimulated mononuclear supernatants were decreased in autoimmune thyroid disease. It is possible that there is deficient or decreased transduction between activated T cells and IL-2-activated killer cells or activated T cells and cytokine-producing cells in autoimmune thyroid disease to account for these findings. These results suggest that IL-2-induced hypothyroidism in vivo might not be associated with preexisting autoimmune thyroid disease, since in these studies, thyrocytes from normal persons (rather than from autoimmune thyroid disease) have a susceptibility to the lysing effects of IL-2 and IL-2-activated killer cells.