Cytophilic anti-thyroglobulin antibody and antibody-dependent macrophage-mediated cytotoxicity in Hashimoto's thyroiditis.

ABSTRACT

Antibody-dependent macrophage-mediated cytotoxicity was studied to determine the significance of cytophilic anti-thyroglobulin antibody (ATgA) present in the sera of patients with Hashimoto's thyroiditis. Effector cells were normal human monocytes or guinea-pig peritoneal exudate cells, and target cells were human thyroglobulin(Tg)-coated chicken erythrocytes. Cytotoxicity was evaluated by morphological observation and by 51Cr-releasing assay. Normal human monocytes rapidly destroyed ATgA-bound Tg-coated chicken erythrocytes by extracellular cytolysis and by phagocytosis. On the contrary, human monocytes "armed" with cytophilic ATgA destroyed Tg-coated chicken erythrocytes slowly and to a lesser extent, and only by extracellular cytolysis. When normal monocytes or peritoneal exudate cells were incubated with Tg-coated chicken erythrocytes in the presence of the sera of patients with Hashimoto's thyroiditis, phagocytosis occurred rapidly, but extracellular cytolysis developed rather slowly. These data suggest the possibility that human monocytes participate in antibody-dependent cell-mediated cytotoxicity (ADCC) in vivo, which may be an important destructive mechanism in Hashimoto's thyroiditis. It is also possible that ATgA cytophilic for monocytes render non-immune peripheral monocytes cytotoxic against Tg-bearing cells.