ADHESION MOLECULES FROM THE LFA-1 ICAM-1,3 AND VLA-4/VCAM-1 PATHWAYS ON T-LYMPHOCYTES AND VASCULAR ENDOTHELIUM IN GRAVES AND HASHIMOTOS THYROID-GLANDS/

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid di sorders requires, as a first step, their attachment to endothelial cel ls (EC) and, subsequently, their interaction with thyrocytes and extra cellular matrix proteins. A number of different ligand molecules have been identified to mediate the interaction between EC and leukocyte su bpopulations. In this study, we examined by flow cytometry and immunoh istochemical techniques, the expression of integrin receptors and thei r counter-receptors by infiltrating lymphocytes and vascular endotheli um in thyroid glands from patients with Graves' disease (GD) and Hashi moto's thyroiditis (HT). A high proportion of GD intrathyroidal T lymp hocytes expressed the CD69 and gp95/85 (Ea2) activation antigens as we ll as an increased number of LFA-alpha(L), VLA-alpha 1, -alpha 4, -alp ha 5, and -beta 1 integrin receptors, as compared with peripheral bloo d T lymphocytes from the same patients. The expression of intercellula r adhesion molecule (ICAM)-1 was increased in EC from GD and HT thyroi ds. In addition, an up-regulated de novo expression of vascular cell a dhesion molecule (VCAM)-1 was found in EC in GD and HT thyroids, with no reactivity in control thyroids. Dendritic cells in thyroid lymphoid follicles were also positive for ICAM-1 and VCAM-1. In addition, most of intrathyroidal mononuclear cells expressed the ICAM-3 adhesion mol ecule. This enhanced expression of ICAM-1 and VCAM-1 by thyroid EC in GD and HT may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules . Our data suggest that both the LFA-1/ICAM-1, ICAM-3 and VLA-4/VCAM-1 pathways could play a relevant role in localizing and perpetuating th e autoimmune response in the thyroid gland in autoimmune thyroid disor ders.