Interferon-mediated enhancement of thyroid major histocompatibility complex antigen expression. A flow cytometric analysis.
Epithelial expression of class II antigens encoded by the major histocompatibility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL-5), which constitutively expresses class I (OX18) but not class II (OX6 or OX17) determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat gamma interferon (rIFN-gamma) induced dose-dependent expression of OX6 (I-A) antigen at greater than 48 h (maximum 80-90% of cells in culture at 100 U/ml), which was abrogated by DB-1, a monoclonal antibody to rat IFN-gamma. OX17 antigen (I-E) was also induced (86%) and OX18 (class I) markedly increased under these conditions. Other thyroid-active agents including the calcium ionophore A23187, dibutyryl cyclic AMP, thyroid-stimulating autoantibodies from Graves' disease patients (LATS), and TSH, caused no I-A induction. Supernatants from spleen cells stimulated with plant lectins (concanavalin A or phytohaemagglutinin), but not lectin alone, evoked substantial class II induction, which was inhibited by DB-1. These findings suggest that IFN-gamma is the central mediator of thyroid epithelial class II expression. FRTL-5 provides a powerful model for the analysis of thyroid MHC class II dynamics and a potential means of analysing the role of epithelial class II in autoimmune pathogenesis.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D037102:Lectins / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013961:Thyroid Gland / Q000276:immunology*
D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D037102:Lectins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007372:Interferons