T-dependent destruction of thyroid isografts exposed to IFN-gamma.
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-gamma and then transplanted to adult isogeneic recipients. The thyroid that had been induced to express class II genes by IFN-gamma 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-gamma nor expression of class II genes compromised the thyroid. Thus, in some tissues, exposure to IFN-gamma and/or the induction of class II expression can lead to T-dependent autoimmune disease.
Frohman
M
M
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Francfort
J W
JW
Cowing
C
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude / Q000276:immunology; D009924:Organ Culture Techniques; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology* / Q000637:transplantation; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma