EFFECTS OF RECOMBINANT HUMAN INTERFERON-GAMMA ON HUMAN THYROID TISSUES FROM PATIENTS WITH GRAVES-DISEASE AND NORMAL SUBJECTS TRANSPLANTED INTO NUDE-MICE

We have attempted to determine whether inferferon gamma (IFN-gamma) would enhance, sustain or induce autoimmune thyroid disease (AITD) in xenotransplanted thyroid tissue from patients with Graves' disease or normal persons (actually paranodular tissue) in nude athymic mice, in the absence of an intact immune system. A dosage of 4000 U/mouse of human IFN-gamma(hIFN-gamma) was injected intraperitoneally daily for six consecutive weeks into the xenotransplanted mice. The parameters measured included the free T4 index, thyroid autoantibodies and TSH during the course of hIFN-gamma injections. Thyroid epithelial cell (TEC) HLA-DR expression was measured in the thyroid tissue before xenotransplantation and at sacrifice; in addition, light and electron microscopic studies were carried out at those times. There were no significant differences in thyroid function between the control results and those obtained with hIFN-gamma in either group of tissues. TEC HLA-DR expression was significantly increased by hIFN-gamma in the normal group, but insignificantly in the Graves' group. In both light and electron microscopic observations, Graves' tissue (whether or not treated with hIFN-gamma) was indistinguishable at sacrifice from normal thyroid tissue. The appearance had markedly altered from the same Graves' tissue examined at the time of the initial human surgery, which then showed the usual histological appearance of this disorder. We conclude that IFN-gamma induced HLA-DR expression alone is not sufficient to sustain the ongoing process of AITD in this model. Graves' TEC appear to be essentially normal when removed from their immune environment; it may be proposed that TEC may be mere passive captives to immunologic events in terms of the pathogenesis of AITD, without any intrinsic functional abnormality.