Newer insights into the pathogenesis of experimental autoimmune thyroiditis

E. A. Stafford, N. R. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental autoimmune thyroiditis (EAT), produced in the mouse by immunization with murine thyroglobulin plus complete Freund's adjuvant, represents a valuable model for studying the pathogenesis of human chronic (Hashimoto's) thyroiditis. A major issue requiring clarification is the difference between benign autoimmunity, characterized solely by production of autoantibodies to thyroglobulin, and pathogenic autoimmunity where injury occurs to the thyroid cells. In this article, we describe the role of two key cytokines, IL12 and IFNγ, in modifying the pathogenic immune response. EAT, defined by cellular infiltration of the thyroid and the development of thyroglobulin-specific autoantibodies, is a dynamic process. Consequently, a cytokine may exert a different effect at different times during the disease process. For purposes of discussion, we propose that there are three stages in the development of EAT: priming; initiation; and progression. Administration of anti-IL12 during the priming stage and initiation dramatically decreases disease and lowers autoantibody levels. In contrast, injection of recombinant IL12 after disease was established significantly decreases the severity of disease and reduces autoantibody levels. Unlike IL-12, IFNγ was not essential for the priming of EAT. However, the severity of disease in the anti-IFNγ-treated initiation-and progression-treated animals was higher than in controls, implying a regulatory role for IFNγ. These findings emphasize that EAT involves a complex array of pathogenic mechanisms. The balance of cytokines produced during the early phase of the autoimmune reaction probably determines the progression from a harmless autoimmune response to autoimmune disease.

Original languageEnglish (US)
Pages (from-to)501-533
Number of pages33
JournalInternational Reviews of Immunology
Volume19
Issue number6
DOIs
StatePublished - 2000

Keywords

  • Cytokines
  • IFN-γ
  • IL-12
  • Thyroglobulin
  • Thyroiditis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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