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.