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).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040721-02
Application #
3241140
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1988-05-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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