Characterization of a novel H2A-E+ transgenic model susceptible to heterologous but not self thyroglobulin in autoimmune thyroiditis: Thyroiditis transfer with Vβ8+ T cells

Yan Yan, John C. Panos, Daniel J. McCormick, Qiang Wan, Alvaro A. Giraldo, Vladimir Brusic, Chella S. David, Yi Chi M. Kong

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Recently we reported on a novel H2E transgenic, IA-negative model of experimental autoimmune thyroiditis (EAT) that excludes reactivity to self in its susceptibility pattern to heterologous thyroglobulin (Tg). In conventional, susceptible mouse strains, EAT is inducible with both homologous and heterologous Tg; e.g., human (h)Tg shares conserved thyroiditogenic epitopes with mouse (m)Tg. However, when an H2Eak transgene is introduced into class II-negative B10.Ab0 mice, which express neither surface IA (mutant Aβ-chain) nor surface IE (nonfunctional Ea gene), the resultant H2Eb molecules are permissive for EAT induction by hTg, but not self mTg. Also, the hTg-primed cells do not cross-react with mTg. To explore this unique capacity of E+B10.Ab0 mice to distinguish self from nonself Tg, we have developed T cell lines to examine the T cell receptor repertoire and observed a consistent Vβ8+ component after repeated hTg stimulation. Enrichment and activation of Vβ8+ T cells by either superantigen staphylococcal entertoxin B or anti-Vβ8 in vitro enabled thyroiditis transfer to untreated A-E+ recipients, similar to hTg activation. Vβ8+ T cells isolated by FACS from hTg-immunized mice also proliferated to hTg in vitro. These studies support the contribution of Vβ8 genes to the pathogenicity of hTg in this H2A-E+ transgenic model.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalCellular Immunology
Volume212
Issue number1
DOIs
StatePublished - Aug 25 2001

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Keywords

  • Autoimmune thyroiditis
  • Autoimmunity
  • EAT
  • H2E transgene in EAT
  • Human thyroglobulin
  • TCRBV usage
  • Vβ8 T cells

ASJC Scopus subject areas

  • Immunology

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