Experimental thyroiditis in the rhesus monkey. I. Cytotoxic, mixed-agglutinating and complement-fixing antibodies

Abstract

Rhesus monkeys inoculated repeatedly with a crude extract of pooled rhesus thyroids plus complete Freund adjuvant produced autoantibodies cytotoxic for monkey and human thyroid cells in vitro. No cytotoxicity was observed with normal rhesus kidney or adrenal cells taken as controls from the same animals. The specific cytotoxic reaction was absorbed by thyroid microsomes, but not by other tissue fractions. Monkey (as well as human) thyroiditis sera failed to fix complement with thyroglobulin although both fixed complement with crude thyroid suspensions. The cytotoxic antibody was heat stable (56°C for 30 min) and required complement for damage to tissue cells. Fractionation by sucrose gradient ultracentrifugation demonstrated that the cytotoxic antibody had a sedimentation rate of about 7S and was stable to sulphydryl agents, whereas the complement-fixing antibody sedimented more rapidly and was largely inactivated by mercaptoethanol treatment. Thus in this case, cytotoxic antibody is not identical with the over-all complement-fixing activity of an antiserum. The presence of organ specific antigen on the surface of cultured rhesus thyroid cells was detected by the mixed agglutination antiglobulin reaction using monkey antisera. The curves of antibody production detected by mixed agglutination and cytotoxicity tend to correspond although the former test was 10–100 times more sensitive.