IFN-gamma has a protective role against thyroid-specific autoantibody production in severe combined immunodeficient (SCID) mice xenografted with Graves' thyroid tissue.

Abstract

We studied the effects of exogenous human IFN-gamma or neutralizing monoclonal antibody (mAb) to IFN-gamma on xenografted human Graves' thyroid tissue in severe combined immunodeficient (SCID) mice to investigate a possible role of IFN-gamma in the pathogenesis of human Graves' disease. Human thyroid tissues from four patients with Graves' disease were xenografted into SCID mice. Two weeks after xenografting, mice were divided into three groups with human IgG levels similar to each other. Mice in the first group were treated with human IFN-gamma daily for 6 weeks; mice in the second (similar) group were treated with an mAb to IFN-gamma; mice in the third group were given mouse IgG only (control group). Blood samples were taken every 2 weeks for human IgG and thyroid-specific autoantibodies (Tg-Ab, TPO-Ab, and thyroid-stimulating antibody). After 6 weeks' treatment, mice were killed, and the thyroid xenograft was examined for thyrocyte HLA-DR expression. Human IgGs were produced equally in all three groups; mice treated with IFN-gamma showed significantly lower amounts of thyroid autoantibodies than those in the control group. Thyrocyte HLA-DR expression was markedly increased in xenografts from mice with IFN-gamma administration. On the other hand, anti-IFN-gamma mAb injection caused only slight suppression of HLA-DR expression on xenografted thyroid cells. In conclusion, IFN-gamma may down-regulate the production of thyroid-specific autoantibodies but not human IgG, at least under these circumstances; there thus may be specific inhibitory effects of IFN-gamma against thyroid-specific autoantibody production of intrathyroidal plasma cells, and this animal model may help to elucidate the possible role of cytokines in the pathogenesis of Graves' disease.