IFN-GAMMA HAS A PROTECTIVE ROLE AGAINST THYROID-SPECIFIC AUTOANTIBODYPRODUCTION IN SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE XENOGRAFTEDWITH GRAVES THYROID-TISSUE

We studied the effects of exogenous human IFN-gamma or neutralizing mo noclonal antibody (mAb) to IFN-gamma on xenografted human Graves' thyr oid tissue in severe combined immunodeficient (SCID) mice to investiga te a possible role of IFN-gamma in the pathogenesis of human Graves' d isease. Human thyroid tissues from four patients with Graves' disease were xenografted into SCID mice. Two weeks after xenografting, mice we re divided into three groups with human IgG levels similar to each oth er. Mice in the first group were treated with human IFN-gamma daily fo r 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 (cont rol group). Blood samples were taken every 2 weeks for human IgG and t hyroid-specific autoantibodies (Tg-Ab, TPO-Ab, and thyroid-stimulating antibody). After 6 weeks' treatment, mice were killed, and the thyroi d xenograft was examined for thyrocyte HLA-DR expression. Human IgGs w ere produced equally in all three groups; mice treated with IFN-gamma showed significantly lower amounts of thyroid autoantibodies than thos e in the control group. Thyrocyte HLA-DR expression was markedly incre ased in xenografts from mice with IFN-gamma administration. On the oth er hand, anti-IFN-gamma mAb injection caused only slight suppression o f HLA-DR expression on xenografted thyroid cells. In conclusion, IFN-g amma may down-regulate the production of thyroid-specific autoantibodi es but not human IgG, at least under these circumstances; there thus m ay be specific inhibitory effects of IFN-gamma against thyroid-specifi c autoantibody production of intrathyroidal plasma cells, and this ani mal model may help to elucidate the possible role of cytokines in the pathogenesis of Graves' disease.