IFN-γ-Deficient Mice Develop Severe Granulomatous Experimental Autoimmune Thyroiditis with Eosinophil Infiltration in Thyroids

Abstract

AbstractTo study the role of IFN-γ in the development of granulomatous experimental autoimmune thyroiditis (EAT), DBA1 mice with a disrupted IFN-γ gene were used for adoptive EAT induction. Effector cells from either IFN-γ+/+ or IFN-γ−/− donor mice activated with mouse thyroglobulin and anti-IL-2R mAb induced severe granulomatous EAT. A predominant infiltration of the thyroid by eosinophils was observed in recipients of IFN-γ−/− effector cells but not in recipients of IFN-γ+/+ cells. Compared with wild-type mice, thyroids of recipients of IFN-γ−/− effector cells had decreased expression of mRNA for Th1 cytokines and inducible nitric oxide synthetase. Expression of Th2 cytokine mRNA was comparable to that of IFN-γ+/+ mice, and expression of eotaxin was increased in the thyroids of recipients of IFN-γ−/− effector cells. Activation of cells from either IFN-γ+/+ or IFN-γ−/− donors in the presence of IL-12 also induced severe granulomatous EAT. Eosinophil infiltration in recipients of IFN-γ−/− cells was unaffected when effector cells were activated with IL-12, and thyroids expressed predominantly Th2 cytokines. The extent of fibrosis of recipient thyroids was generally greater when donor IFN-γ+/+ and IFN-γ−/− cells were activated with IL-12. Compared with IFN-γ+/+ mice, IFN-γ−/− mice produced lower levels of mouse thyroglobulin-specific autoantibodies after immunization with MTg and LPS. These results indicate that cells from both IFN-γ+/+ and IFN-γ−/− donors can induce severe granulomatous EAT. However, damage of thyroid follicles by IFN-γ−/− and that by IFN-γ+/+ cells appear to involve different mediators of inflammation.