Experimental autoimmune thyroiditis (EAT) in mice serves as a prototype for the study of Hashimoto's thyroiditis, as well as other organ-specific autoimmune disorders. The overall goal of this project is to use murine EAT to probe the suppressor mechanisms leading to thyroid dysfunction. As in the human, the autoimmune response is under genetic control. A major thyroid antigen is thyroglobulin (Tg) which can be used to induce EAT in genetically susceptible strains, linked to the major histocompatibility complex (MHC). Three recent observations from our laboratory have provided impetus to this proposal: 1) Self tolerance strengthened by the prior administration of exogenous MTg to withstand immunogenic challenge is mediated by suppressor T cells; 2) enhanced resistance to EAT induction can also be achieved by physiologic manipulation of circulatory MTg level with thyroid-regulating hormones; and 3) selective in vivo elimination of T cell subsets with highly efficient rat monoclonal antibodies (mAb) to L3T4 and Lyt-2 prevents or modifies EAT induction and development. We propose to: 1. Characterize, both in vitro and in vivo, suppressor T cells activated by the administration of exogenous MTg. 2. Determine the functional capabilities of mAb to L3T4 in enhancing resistance to EAT and re-establishing self tolerance. 3. Examine suppressor mechanisms activated by thyroid-stimulating hormone (TSH).

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Immunological Sciences Study Section (IMS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wayne State University
Schools of Medicine
United States
Zip Code
Fuller, B E; Giraldo, A A; Waldmann, H et al. (1994) Depletion of CD4+ and CD8+ cells eliminates immunologic memory of thyroiditogenicity in murine experimental autoimmune thyroiditis. Autoimmunity 19:161-8
Fuller, B E; Okayasu, I; Simon, L L et al. (1993) Characterization of resistance to murine experimental autoimmune thyroiditis: duration and afferent action of thyroglobulin- and TSH-induced suppression. Clin Immunol Immunopathol 69:60-8
Lewis, M; Fuller, B E; Giraldo, A A et al. (1992) Resistance to experimental autoimmune thyroiditis is correlated with the duration of raised thyroglobulin levels. Clin Immunol Immunopathol 64:197-204
Nabozny, G H; Kong, Y C (1992) Circumvention of the induction of resistance in murine experimental autoimmune thyroiditis by recombinant IL-1 beta. J Immunol 149:1086-92
Nabozny, G H; Flynn, J C; Kong, Y C (1991) Synergism between mouse thyroglobulin- and vaccination-induced suppressor mechanisms in murine experimental autoimmune thyroiditis. Cell Immunol 136:340-8
Nabozny, G H; Cobbold, S P; Waldmann, H et al. (1991) Suppression in murine experimental autoimmune thyroiditis: in vivo inhibition of CD4+ T cell-mediated resistance by a nondepleting rat CD4 monoclonal antibody. Cell Immunol 138:185-96
Flynn, J C; Kong, Y C (1991) In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis. Clin Immunol Immunopathol 60:484-94
Conaway, D H; Giraldo, A A; David, C S et al. (1990) In situ analysis of T cell subset composition in experimental autoimmune thyroiditis after adoptive transfer of activated spleen cells. Cell Immunol 125:247-53
Nabozny, G H; Simon, L L; Kong, Y C (1990) Suppression in experimental autoimmune thyroiditis: the role of unique and shared determinants on mouse thyroglobulin in self-tolerance. Cell Immunol 131:140-9
Conaway, D H; Giraldo, A A; David, C S et al. (1989) In situ kinetic analysis of thyroid lymphocyte infiltrate in mice developing experimental autoimmune thyroiditis. Clin Immunol Immunopathol 53:346-53

Showing the most recent 10 out of 13 publications