EXPERIMENTAL AUTOIMMUNE-THYROIDITIS (EAT) IN MICE LACKING THE IFN-GAMMA RECEPTOR GENE

To investigate the role of interferon-gamma (IFN-gamma) in experimenta l autoimmune thyroidits (EAT), H-2(k) mice with a disrupted IFN-gamma receptor (IFN-gamma R) gene were immunized with porcine thyroglobulin (pTg). We observed that EAT occurred on day 19 and remitted on day 35 in IFN-gamma R-deficient (IFN-gamma R-0/0) mice, whereas in wild-type mice, EAT occurred on day 21 and remitted on day 42-49. Moreover, EAT in the mutant mice was attenuated and accompanied by diminished Tg-spe cific cytotoxic and proliferative responses and decreased titers of an ti-Tg antibodies, notably of the IgG2a and IgG2b isotypes. In contrast , Tg-specific IgG1 was increased in the IFN-gamma R-0/0 mice. In super natants from T cells further stimulated in vitro by Tg, IFN-gamma leve ls were higher in IFN-gamma R-0/0 than in wild-type mice throughout th e course of the disease, whereas interleukin-10 was transiently increa sed prior to EAT onset in both groups of mice. Finally, using IFN-gamm a R-0/0 mice, we demonstrate that induction of EAT does not require an intact IFN-gamma system, while progression to full-blown disease depe nds on the action of IFN-gamma.