Induction of experimental autoimmune thyroiditis in IL-12(-/-) mice

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by tra nsfer of mouse thyroglobulin (MTg)-sensitized spleen cells activated in vit ro with MTg and anti-IL-2R or MTg and IL-12. Previous work suggested that I L-12 was required in vitro for development of G-EAT. To determine whether I L-12 was also required during the induction and/or effector phases, DBA/1 m ice with a disrupted IL-12-P40 gene (IL-12(-/-)) were used for EAT inductio n. Cells from MTg-sensitized IL12(-/-) donors activated in vitro by MTg or MTg and anti-IL2R induced severe EAT in recipient mice. Compared with effec tor cells from IL-12(+/+) donors, effector cells from IL-12(-/-) donors ind uced thyroid lesions dominated by lymphocytes with minimal granulomatous ch anges. Thyroids of recipients of IL-12(-/-) cells expressed less IFN-gamma mRNA and more TGF-beta, IL-4, and IL-10 compared with recipients of IL-12(/+) cells. When IL-12 was added during in vitro activation, cells from both IL-12(-/-) and IL-12(+/+) donors induced severe G-EAT, and expression of a ll cytokines except IL-12 was comparable in thyroids of both IL-12(+/+) and IL-12(-/-) recipients. Transfer of cells from IL-12(+/+) or IL-12(-/-) don ors into IL-12(+/+) or IL-12-/- recipients indicated that IL-12 expressed i n thyroids was derived from recipients. Thus, endogenous IL-12 is not absol utely essential for the sensitization and activation of EAT effector cells to induce severe EAT, although it is required in vitro to promote activatio n of cells to induce severe granulomatous histopathology.