title: Induction of human thyroid cell ICAM-1 (CD54) antigen expression and ICAM-1-mediated lymphocyte binding.
abstract: To further understand the mechanism of lymphocyte accumulation within the thyroid gland in autoimmune thyroid disease we have examined the expression, regulation, and functional significance of the intercellular adhesion molecule-1 (ICAM-1, CD54) in human thyroid monolayer cells and immortalized thyroid cell clones. Human thyroid monolayer cells derived from both normal and abnormal human thyroid tissue showed low basal expression of the ICAM-1 antigen by flow cytometric assessment (mean % +/- SD positive cells = 13.7 +/- 6.1) compatible with the presence of ICAM-1 positive nonthyroid cells within the monolayer cultures. However, thyroid cell ICAM-1 antigen expression was further induced by exposure to recombinant human interferon-gamma (IF-gamma). At 100 U/ml, IF-gamma induced ICAM-1 expression in 56.0 +/- 19.0% of thyroid monolayer cells. Even greater expression of ICAM-1 antigen was induced by IF-gamma in human fetal thyroid cell monolayers of high purity (up to 80% of ICAM-1 positivity) thyroid monolayers established from a patient with Graves' disease (up to 84%), and in two immortalized human thyroid cell clones, 12S and TAD-2 (up to 61%). Furthermore, dose-response curves for ICAM-1 and HLA-DR antigen induction by increasing concentrations of IF-gamma showed that ICAM-1 antigen gene induction was 10-fold more responsive to IF-gamma than the HLA-DR antigen gene. In order to explore the functional consequence of ICAM-1 antigen expression by thyroid epithelial cells we examined the binding of peripheral blood mononuclear cells to thyroid monolayer cells and immortalized thyroid cells. These studies revealed a preferential adhesion of human PBMC to IF-gamma-treated thyroid monolayers compared to untreated control monolayer cells. Furthermore, this IF-gamma-induced cell adhesion was specifically inhibited by monoclonal anti-ICAM-1. These experiments demonstrate not only the capacity of human thyroid epithelial cells to express ICAM-1 antigen in the presence of a cytokine but, in addition, identify ICAM-1 antigen as responsible for enhanced T cell binding to thyroid epithelial cells. ICAM-1 antigen may, therefore, play an important role in T cell targeting and accumulation within the thyroid gland in autoimmune thyroid disease.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: G K
authors.initials: GK
authors.lastname: Huber
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013959:Thyroid Diseases / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma