Expression of Intracellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 and Homing Factor CD44 After Engraftment of Graves' Lymphocytes in Xenotransplanted Human Thyroid Tissue in Athymic Nude Mice

Abstract

The expression of adhesion molecules on thyrocytes and endothelium cells plays an important role in the pathogenesis of Graves' disease (GD). The intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1), and the homing receptor CD44 are responsible for the specific migration of lymphocytes in autoimmune thyroid diseases (AITD) (homing). Eight weeks after transplantation of thyroid tissue from 26 patients with nonautoimmune thyroid disease (nontoxic nodular goiter [NTG]) into nude mice, peripheral (PBL) and intrathyroidal lymphocytes (ITL) from 14 patients with NTG and 12 patients with GD were grafted into the animals. Two days after lymphocyte engraftment, the thyroid transplants were examined histologically (HE) and immunohistologically stained with monoclonal antibodies directed against ICAM-1, VCAM-1, and CD44. After injection of GD lymphocytes, thyroid transplants expressed significantly more ICAM-1, VCAM-1, and CD44 than after injection of NTG lymphocytes. This expression was even more pronounced after grafting of GD intrathyroidal lymphocytes. Our data demonstrate that only GD lymphocytes induce the expression of adhesion molecules and homing factor CD44, both of which play an important role in the migration of lymphocytes and induction of the autoimmune process.

Autoimmune thyroid disease: propagation and progression

“…Perhaps more significantly, thyroid cell expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) is enhanced by g-IFN, tumour necrosis factor (TNF) and interleukin-1 (IL-1), which can be shown to have a direct enhancing effect on both cytotoxicity and other interactions with lymphocytes, as both molecules are important in the binding of lymphocytes to targets (36,37). Others have shown that thyroid cells express CD44 which acts as a homing receptor for hyaluronan, mediates leukocyte rolling, the first step in tissue homing, and may (like ICAM-1) induce lymphocyte activation under certain circumstances; expression of CD44 by thyrocytes is presumably also altered by cytokines as lymphocytes can upregulate expression (38).…”

Cellular immune responses in autoimmune thyroid disease

“…Cutaneous lymphocyte-associated antigen, a selectin found on high endothelial venules, occurs on the endothelium in AITD thyroid tissue (Armengol et al ., 2001). β 1 -integrins mediate cell attachment to extracellular matrix proteins and one of these, VLA-α 2 (very late antigen-α 2), is upregulated on endothelial cells in AITD, as are vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-and P-selectins (Marazuela et al ., 1995(Marazuela et al ., , 1997Jungheim et al ., 2001). Interestingly, the increased intrathyroidal vasculature which typifies Graves' disease is associated with an increase in circulating vascular endothelial growth factor, which appears to be derived from the thyroid cells in response to TSH-R stimulation by TSH-R stimulating antibodies (Iitaka et al ., 1998).…”

Endokrinologie—Teil II

“…Autoimmunerkrankungen der Schilddrüse sind häufigste Ursache von Funktionsstörungen (Hyper-, Hypothyreosen). Die differenzierte Untersuchung pathogenetischer und pathophysiologischer Zusammenhänge dieser Autoimmunthyreopathien eröffnet diagnostisch und therapeutisch neue Ansatzpunkte der Behandlung [69][70][71][72].…”

“…im retroorbitalen Gewebe), mit der Blockade von spezifischen Zytokinen oder Adhäsions-molekülen oder der Blockierung z.B. des TSH-Rezeptors mit spezifischen Antikörpern [69,70]. …”