The role of alpha 4 integrin and intercellular adhesion molecule-1 (ICAM-1) in murine experimental autoimmune thyroiditis.
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 alpha 4 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 alpha 4 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-alpha 4 and anti-ICAM mAb administration on EAT severity in recipient mice was also determined. Anti-alpha 4 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 alpha 4-VCAM interactions may be of particular importance in trafficking of effector cells to the thyroid.
McMurray
R W
RW
Department of Internal Medicine, University of Missouri, Columbia 65212, USA.
Tang
H
H
Braley-Mullen
H
H
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism; D007116:Immunization, Passive; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*
D015703:Antigens, CD; D018960:Hyaluronan Receptors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D013954:Thyroglobulin