The Role of α4 Integrin and Intercellular Adhesion Molecule-1 (ICAM-1) in Murine Experimental Autoimmune Thyroiditis

Abstract

Mouse-thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induce a lymphocytic form of experimental autoimmune thyroiditis (EAT) whereas activation of the same cell population with MTg in the presence of anti-interleukin 2 receptor antibody (M7/20) induces a granulomatous form of EAT. The thyroid infiltrate in both lymphocytic and granulomatous EAT includes both CD4 + and CD8 + T cells and CD4 + T cells are the primary effector cells for both forms of EAT. This investigation was undertaken to begin to define the roles of α4 integrin, and intercellular adhesion molecule-1 (ICAM-1) in the migration of CD4+ and CD8 + T cells to the thyroid in EAT. The studies presented here demonstrate the expression of α4 integrin and ICAM-1 on CD4 + and CD8 + T cells infiltrating the thyroid and the expression of vascular cell adhesion molecule (VCAM) and ICAM-1 on thyroid cells of mice with EAT. The effects of anti-α4 and anti-ICAM mAb administration on EAT severity in recipient mice was also determined. Anti-α4 administration reduced or abolished lymphocyte infiltration in the thyroid resulting in reduced severity of both lymphocytic and granulomatous EAT. In contrast, anti-ICAM mAb had little effect on EAT severity. These results suggest that these two adhesion molecules exhibit differential functional roles in the modulation of EAT disease severity and that α4-VCAM interactions may be of particular importance in trafficking of effector cells to the thyroid.

Key Words:

• autoimmune thyroiditis
• adhesion molecules