IFN-GAMMA-DEFICIENT MICE DEVELOP SEVERE GRANULOMATOUS EXPERIMENTAL AUTOIMMUNE-THYROIDITIS WITH EOSINOPHIL INFILTRATION IN THYROIDS

To study the role of IFN-gamma in the development of granulomatous exp erimental autoimmune thyroiditis (EAT), DBA1 mice with a disrupted IFN -gamma gene were used for adoptive EAT induction, Effector cells from either IFN-gamma(+/+) or IFN gamma(-/-) donor mice activated with mous e thyroglobulin and anti-IL-2R mAb induced severe granulomatous EAT. A predominant infiltration of the thyroid by eosinophils was observed i n recipients of IFN-gamma(-/-) effector cells but not in recipients of IFN-gamma(+/+) cells, Compared with wild-type mice, thyroids of recip ients of IFN-gamma(-/-) effector cells had decreased expression of mRN A for Th1 cytokines and inducible nitric oxide synthetase, Expression of Th2 cytokine mRNA was comparable to that of IFN-gamma(+/+) mice, an d expression of eotaxin was increased in the thyroids of recipients of IFN-gamma(-/-) effector cells. Activation of cells from either IFN-ga mma(+/+) or IFN-gamma(-/-) donors in the presence of IL-12 also induce d severe granulomatous EAT. Eosinophil infiltration in recipients of I FN-gamma(-/-) cells was unaffected when effector cells were activated with IL-12, and thyroids expressed Predominantly Th2 cytokines, The ex tent of fibrosis of recipient thyroids was generally greater when dono r IFN-gamma(+/+) and IFN-gamma(-/-) cells were activated with IL-12, C ompared with IFN-gamma(+/+) mice, IFN-gamma(-/-) mice produced lower l evels of mouse thyroglobulin-specific autoantibodies after immunizatio n with MTg and LPS, These results indicate that cells from both LFN-ga mma(+/+) and IFN-gamma(-/-) donors can induce severe granulomatous EAT , However, damage of thyroid follicles by IFN-gamma(-/-) and that by I FN-gamma(+/+) cells appear to involve different mediators of inflammat ion.