Experimental autoimmune thyroiditis in mice is a very useful model of autoimmune disease since it shows the strongest genetic control by gene(s) within the major histocompatibility complex so far described for such a disease. Preliminary experiments suggested that monoclonal anti-Ia antibodies given before immunization of mice with mouse thyroglobulin emulsified in complete Freund's adjuvant, completely prevented the development of thyroiditis. These experiments will be expanded, giving antibodies after the immunization, to observe a suppressive effect on the established disease. The minimum amount of monoclonal antibody needed for suppression and the effect of several antibodies directed against different Ia antigens will be investigated to show the particular Ia antigen(s) on antigen presenting cells involved in presenting thyroglobulin to T lymphocytes. In mice given monoclonal anti-Ia and immunized with thyroglobulin in Freund's adjuvant, several parameters will be monitored namely, the in vitro lymphocyte stimulation by thyroglobulin, the number of T and B lymphocytes (and the number of their subsets) in the spleen, the number of plaque forming cells in the spleen, the skin delayed-type hypersensitivity reaction after challenge with thyroglobulin, the titer of circulating thyroglobulin antibodies, the IgG concentration in serum, the number of cytotoxic T lymphocytes in lymph nodes, and the magnitude of thyroid infiltration with mononuclear cells. Adoptive transfer experiments will be performed to detect the possible induction of suppressor cells after treatment with monoclonal anti-Ia. The expression of Ig antigens in the thyroid of mice (on thyroid cells, antigen presenting cells and endothelial cells) during the development of EAT and the possible modulation of Ia antigens by anti-Ia antibody will be investigated by immunofluorescence and electron microscopy. The effect of various monoclonal anti-Ia antibodies on in vitro lymphocyte stimulation by thyroglobulin will also be investigated in mice immunized with thyroglobulin. The experiments just described will shed light on the role of class II major histocompatibility antigens in the development of autoimmune diseases and will help to better understand the genetic control of these diseases. The experiments will also suggest methods for specific treatment of human autoimmune diseases.
| Vladutiu, A O (1991) Treatment of autoimmune diseases with antibodies to class II major histocompatibility complex antigens. Clin Immunol Immunopathol 61:1-17 |
| Queluz, T H; Pawlowski, I; Brunda, M J et al. (1990) Pathogenesis of an experimental model of Goodpasture's hemorrhagic pneumonitis. J Clin Invest 85:1507-15 |
| Vladutiu, A O; Andres, G A (1989) Circulating immune complexes and kidney lesions following 131I administration in mice with thyroglobulin antibodies. Clin Immunol Immunopathol 52:117-25 |
| Vladutiu, A O (1989) Experimental autoimmune thyroiditis in mice chronically treated from birth with anti-IgM antibodies. Cell Immunol 121:49-59 |
