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Related Experiment Videos

Immunosuppression of thyroiditis

V C Guimaraes1, J Quintans, M E Fisfalen

  • 1Department of Medicine, University of Chicago, Illinois 60637, USA.

Endocrinology
|June 1, 1996
PubMed
Summary

Oral administration of thyroglobulin (TG) induces antigen-specific immune tolerance in mice, suppressing inflammatory responses. This mechanism involves a shift to regulatory T cells producing immunosuppressive cytokines, offering insights into autoimmune disease treatment.

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Area of Science:

  • Immunology
  • Endocrinology
  • Autoimmunity

Background:

  • Immunization with human thyroglobulin (TG) induces experimental autoimmune thyroiditis in mice, characterized by thyroid inflammation and anti-TG antibody production.
  • Oral administration of antigens can induce immune tolerance, a phenomenon with potential therapeutic applications in autoimmune diseases.
  • The precise mechanisms underlying antigen-specific oral tolerization remain incompletely understood.

Purpose of the Study:

  • To elucidate the cellular and molecular mechanisms responsible for antigen-specific oral tolerization induced by thyroglobulin (TG) in a mouse model.
  • To investigate the role of cytokine profiles and T cell subsets in mediating oral tolerance.
  • To explore the potential relevance of this model to human autoimmune thyroid disease.

Main Methods:

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  • Mice were immunized with TG to induce thyroiditis and immune responses.
  • Oral administration of TG was employed before and after immunization to induce tolerance.
  • Immune responses, including antibody production, lymphocyte proliferation, and cytokine profiles (IL-2, IFN-γ, IL-4, TGF-β), were assessed in lymphoid organs (PLN, MLN, spleen).

Main Results:

  • Oral TG administration significantly suppressed immune responses to TG, including antibody production and lymphocyte proliferation, in a dose-dependent and antigen-specific manner.
  • Tolerized animals exhibited reduced lymph node size and a distinct cytokine profile, characterized by increased IL-4 and TGF-β production and decreased IL-2 and IFN-γ.
  • CD8+ T cells from tolerized animals produced IL-4 and TGF-β and induced suppression, while CD4+ T cells produced IL-2 and IFN-γ.

Conclusions:

  • Oral tolerization with TG shifts the immune response from a Th-1 to a Th-2/immunosuppressive phenotype, mediated by regulatory T cells.
  • These regulatory cells, induced by oral antigen exposure, migrate to lymphoid tissues and suppress specific and non-specific immune responses.
  • This experimental model provides valuable insights into the mechanisms of oral tolerance and its potential application in managing autoimmune thyroid diseases.