The expression and role in T cell adhesion of LFA-3 and ICAM-2 on human thyroid cells.
Thyroid follicular cells from patients with Graves' disease and Hashimoto's thyroiditis express intercellular adhesion molecule-1 (ICAM-1) and this is in part responsible for T cell adherence in vitro. To assess the potential role of other adhesion molecules in autoimmune thyroiditis, we investigated the expression and function of lymphocyte function-associated antigen-3 (LFA-3) and ICAM-2 on thyroid cells. Under basal culture conditions, a mean of 22.7% of Graves' thyroid cells (n = 8) expressed LFA-3 and this was enhanced by a mixture of T cell-derived cytokines and by IL-1, but not by TSH. LFA-3 was also demonstrated on Graves' (n = 4) and Hashimoto (n = 2) thyroid cells by immunohistochemical staining ex vivo. A small number of thyroid cells (mean 5.5%, n = 5) expressed ICAM-2 by flow cytometry but this was not altered by cytokines, and ICAM-2 could only be demonstrated on endothelial cells by immunohistochemical staining. It seems likely that contamination of primary thyroid cultures by such cells accounted for the small number of ICAM-2+ cells found using flow cytometry. Almost all of the cultured cells expressing LFA-3 or ICAM-2 also expressed ICAM-1, as assessed by dual staining. Blocking LFA-1, LFA-3, and ICAM-1 with monoclonal antibodies inhibited the adherence of T cells to thyroid follicular cells in assays of cell clustering; antibodies against ICAM-2 had no effect. These results show that two important adhesion receptor ligands, ICAM-1 and LFA-3, are expressed by thyroid cells in autoimmune thyroiditis and that these are likely to have functional importance in allowing T cells to bind to thyroid cell targets. This may play an important role in the initiation and maintenance of Graves' disease and Hashimoto's thyroiditis.
Tandon
N
N
Department of Medicine, University of Sheffield, Northern General Hospital, United Kingdom.
Makgoba
M W
MW
Gahmberg
C G
CG
Weetman
A P
AP
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism*; D018968:CD58 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D008562:Membrane Glycoproteins