STUDIES ON THYROID IMMUNITY VII. SPLENECTOMY AND MONKEY IMMUNE THYROIDITIS: THYROIDAL FUNCTION AND THYROXINE TRANSPORT.

The role of the spleen in humoral antibody formation and in the pathogenesis of immune thyroiditis was studied by splenectomizing four monkeys (Macaca mulatta) prior to thyroid isoimmunization. Splenectomized animals, as well as intact controls, were subjected to sequential immunizations and the course of the immune disease was followed by periodic thyroid biopsies and frequent humoral antibody measurements over a period exceeding 1 yr. Extirpation of the secondary lymphoid organ markedly inhibited agglutinating antibody response, prevented formation of complement-fixing antibodies, but had no effect on thyrocytotoxic antibodies. In animals subjected to immunization in complete adjuvant a trend towards a decrease in serum complement levels was evident at the terminal stages of the experiments. Despite the inhibitory effects on some immunological parameters, splenectomy in monkeys prior to thyroid isoimmunization did not interfere with the initiation and progression of pathological processes in the thyroid. Indeed in all splenectomized animals immunized with thyroid plus complete adjuvant, fibrotic thyroid lesions (4+) with virtual obliteration of thyroid follicles were evident, in some as early as 120 days after primary immunization; in contrast, non-fibrotic and less severe lesions were noted in the intact animal despite being repeatedly subjected to similar immunization procedures over a period of 340 days. Immunization in the absence of complete adjuvant did not induce thyroid lesions in the presence or absence of spleen. In all animals with severe thyroid lesions, thyroid function decreased as revealed by T4 and 131I-T3 resin uptake measurements. Paper electrophoresis of serum specimens from a monkey subjected to thyroid isoimmunization in complete adjuvant (and after equilibration with 125I-T4) showed a pronounced retention of 125I-T4 radioactivity at the gamma globulin region indicating formation of antibodies to thyroxine. On the other hand, in sera with a low thyroid antibody titre as in splenectomized monkeys or in those animals immunized within complete adjuvant, T4-binding antibodies were not evident. It is concluded that removal of the spleen prior to thyroid isoimmunization in monkeys, rather than inhibiting the severity of the disease may even aid and abet immunopathogenic events destructive to the thyroid. [ABSTRACT FROM AUTHOR]