title: Ectopic expression of HLA class II antigens on thyroid follicular cells: induction and transfer in vitro by autologous mononuclear leukocytes.
abstract: Ectopic expression of HLA class II antigens by thyroid follicular cells (TFC) might trigger the immune recognition of TFC-specific surface constituents by self-reactive T helper/inducer lymphocytes, with the consequent generation of organ-specific autoimmunity. To explore the alternative possibilities underlying this ectopic expression, i.e. that it either reflects a primary abnormality of the TFC or is secondarily induced by the autoimmune attack itself, we employed immunofluorescence staining of monolayers cultured from thyroid tissue of patients with autoimmune thyroid disease as well as neoplastic, nodular, and normal thyroid tissues to assess the role that autologous mononuclear leukocytes (MNC) and serum factors play in HLA class II induction and modulation in vitro. In all Graves' disease (GD) tissues that initially displayed HLA-DR (DR) antigens, this expression was transient. Primary TFC cultures from tissues with tumor-associated chronic thyroiditis (CT) showed more widespread and persistent DR expression than did cultures from GD tissues. However, in contrast with the findings in GD, there was no correlation between ectopic DR expression on TFC from the CT areas and the presence of organ-specific autoimmune markers. DR expression by TFC was detected in only one of the five nontoxic nodules studied, and involved a small proportion (approximately 20%) of the TFC. A similarly low proportion of DR-positive TFC was found in cultures from two papillary carcinomas, while much stronger DR expression was seen on TFC cultured from the contralateral lobes affected with CT. Only one of four follicular adenomas expressed DR on about 35% of the cultured TFC. In contrast with the rapid extinction of DR expression on TFC cultured from GD tissues after depletion of infiltrated MNC, DR antigen loss did not occur or was significantly delayed when parallel TFC monolayers were cocultured in the presence of autologous MNC from the intrathyroidal infiltrates. Coculture of DR-negative TFC from normal tissues with autologous peripheral blood MNC in individuals without detectable thyroid autosensitization also resulted in pronounced induction of DR expression on the TFC. Purified T lymphocytes from the same peripheral blood MNC preparations, however, did not induce DR expression on these normal TFC. Similarly, MNC obtained from two follicular adenomas, mostly macrophages, did not induce DR expression when cultured with autologous TFC from the same lesions. Addition of 15% autologous serum did not prevent progressive extinction of DR expression on TFC cultured from GD or tumor-associated CT tissues after depletion of infiltrated MNC.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Division of Oral Biology, University of California, San Francisco 94143.
authors.forename: E L
authors.initials: EL
authors.lastname: Khoury
authors.forename: J S
authors.initials: JS
authors.lastname: Greenspan
authors.forename: F S
authors.initials: FS
authors.lastname: Greenspan
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D006680:HLA Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008875:Middle Aged; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001323:Autoantibodies; D006680:HLA Antigens; D006684:HLA-DR Antigens