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Induction of Experimental Autoimmune Thyroiditis in IL-12^-/- Mice¹

Kemin Chen^*, Yongzhong Wei^*, Gordon C. Sharp^*, and Helen Braley-Mullen^2,*,,

Departments of ^* Internal Medicine, Molecular Microbiology and Immunology, and Pathology, School of Medicine, University of Missouri; and Department of Veteran’s Affairs Research Service, Columbia, MO 65212

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by transfer of mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg and anti-IL-2R or MTg and IL-12. Previous work suggested that IL-12 was required in vitro for development of G-EAT. To determine whether IL-12 was also required during the induction and/or effector phases, DBA/1 mice with a disrupted IL-12-P40 gene (IL-12^-/-) were used for EAT induction. Cells from MTg-sensitized IL12^-/- donors activated in vitro by MTg or MTg and anti-IL2R induced severe EAT in recipient mice. Compared with effector cells from IL-12^+/+ donors, effector cells from IL-12^-/- donors induced thyroid lesions dominated by lymphocytes with minimal granulomatous changes. Thyroids of recipients of IL-12^-/- cells expressed less IFN- mRNA and more TGF-, 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 all 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^-/- donors into IL-12^+/+ or IL-12^-/- recipients indicated that IL-12 expressed in thyroids was derived from recipients. Thus, endogenous IL-12 is not absolutely essential for the sensitization and activation of EAT effector cells to induce severe EAT, although it is required in vitro to promote activation of cells to induce severe granulomatous histopathology.

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