T-dependent destruction of thyroid isografts exposed to IFN-γ

Several autoimmune diseases are accompanied by tissue-specific expression of class II molecules of the MHC, and it has been suggested that this elicits a T cell response against tissue-specific Ag to which the individual is not tolerant. However, recent transgenic studies have indicated that non-lymphoid expression of class II genes in the pancreas, liver, and kidney is either innocuous or induces peripheral tolerance. To test this hypothesis in another organ-specific autoimmune disease, we attempted to induce autoimmune thyroiditis in normal mice with class II⁺ thyroid tissue. Normal thyroid lobes were cultured with and without IFN-γ and then transplanted to adult isogeneic recipients. The thyroid that had been induced to express class II genes by IFN-γ was destroyed in normal mice, whereas the control cultured thyroid and the native cervical gland survived. Both types of transplants remained intact and functional in congenic nu/nu recipients, indicating that neither exposure to IFN-γ nor expression of class II genes compromised the thyroid. Thus, in some tissues, exposure to IFN-γ and/or the induction of class II expression can lead to T-dependent autoimmune disease.