Graves' hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice after immunization with thyrotropin receptor DNA

J. C. Flynn, P. V. Rao, M. Gora, G. Alsharabi, W. Wei, A. A. Giraldo, C. S. David, J. P. Banga, Y. M. Kong

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Familial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves' hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7-). DR3+g7- mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalClinical and Experimental Immunology
Volume135
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Class II-knockout
  • DNA vaccination
  • Graves' hyperthyroidism
  • HLA-DR3 transgene
  • Thyrotropin receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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