Enhanced induction of thyroid cell MHC class II antigen expression in rats highly responsive to thyroglobulin.
Initial experiments demonstrated that the degree of autoantibody and proliferative T cell responses to syngeneic rat thyroglobulin differed markedly between Buffalo (high responder) and Fisher (low responder) rats after classical immunization schedules. While varying immune responsiveness may be due to qualitative and quantitative T and B cell differences, the role of thyroid cell MHC class II antigens may be pivotal to the onset of autoimmune thyroiditis in such animal models. We, therefore, examined the induction of MHC class II antigens in thyroid monolayers derived from Buffalo and Fisher rats treated with methimazole (0.1% in their water) for 4 weeks to induce mild thyroid hyperplasia. After thyroidectomy, thyroid cell monolayers were prepared and exposed to recombinant rat gamma-interferon (gamma IF; 10-1000 U/ml) for 1-7 days in the presence and absence of TSH (1 mU/ml). Both Buffalo and Fisher thyroid monolayers responded to gamma IF with MHC class II antigen expression when assessed by laser flow cytometry using MRC OX-6 monoclonal anti-RT1.B. In both types of culture, TSH enhanced MHC class II antigen expression in the presence of gamma IF to the same degree. However, there was a consistently earlier and greater degree of MHC class II antigen expression in Buffalo thyroid monolayers compared to Fisher monolayers, a phenomenon not explicable on the basis of fibroblast contamination as assessed by cytokeratin staining. These data demonstrate that end-organ sensitivity to MHC class II antigen expression may be important in the pathogenesis of autoimmune thyroid disease.
Lahat
N
N
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Hirose
W
W
Davies
T F
TF
D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D000939:Epitopes; D005260:Female; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D051381:Rats; D011915:Rats, Inbred BUF; D011919:Rats, Inbred Strains; D013954:Thyroglobulin / Q000276:immunology / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology; D013972:Thyrotropin / Q000502:physiology
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D013972:Thyrotropin; D013954:Thyroglobulin