Studies have shown that the feeding of antigen orally activates T lymphocytes which can suppress ongoing or induced immunity to the same or closely related antigens. Based upon these findings, it is hypothesized that feeding thyroid stimulating hormone (TSH) receptor, thyroglobulin, or thyroid peroxidase orally might down-modulate the immune reactivity present in Graves' disease or Hashimoto's thyroiditis. In order to test this, a model of Graves' Disease will be developed in mice and the induction of tolerance by oral administration of thyroid stimulating hormone receptor (TSH-R) will be studied. While tolerization to antigen in mice may be quite different from a naturally occurring human response, studies in this model system should provide information on the specificity of tolerance induction, the duration of the tolerant state, the mechanism of the response, and possibly the role of specific T cell epitopes. Ultimately this should help in planning a strategy for use in patients with autoimmune thyroid disease, a disease which causes about 6% of women and 0.6% of men to seek medical attention during their lifetime.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DK009612-04
Application #
6087566
Study Section
Special Emphasis Panel (ZRG2-PSF (04))
Program Officer
Hyde, James F
Project Start
1999-10-15
Project End
Budget Start
1999-10-15
Budget End
2000-10-14
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Wu, L S; Jimmerson, L C; MacBrayne, C E et al. (2016) Modeling Ribavirin-Induced Anemia in Patients with Chronic Hepatitis C Virus. CPT Pharmacometrics Syst Pharmacol 5:65-73
Wu, Liviawati S; Rower, Joseph E; Burton Jr, James R et al. (2015) Population pharmacokinetic modeling of plasma and intracellular ribavirin concentrations in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 59:2179-88
Gardine, C A; Gentile, F; Pellegrini, C et al. (2003) Multiple fragments of human TG are capable of inducing oral tolerance to whole human TG. J Endocrinol Invest 26:294-300
Gardine, C A; Kouki, T; DeGroot, L (2001) Characterization of the T lymphocyte subsets and lymphoid populations involved in the induction of low-dose oral tolerance to human thyroglobulin. Cell Immunol 212:1-15