Flexibility of the thyroiditogenic T cell repertoire for murine autoimmune thyroiditis in CD8-deficient (β2m -/-) and T cell receptor Vβ(c) congenic mice

Lesley C. Lomo, Fusheng Zhang, Daniel J. McCormick, Alvaro A. Giraldo, Chella S. David, Yi Chi M. Kong

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

In murine experimental autoimmune thyroiditis (EAT), previous studies have revealed a highly adaptable thyroiditogenic T cell repertoire which involves both CD4+ and CD8+ T cells in the susceptible H2(k) strain. To further test this flexibility, congenic B10.K mice lacking CD8+ T cells (β2m -/-) or harboring 70% T cell receptor (TCR) Vβ gene deletions (Vβ(c)) were immunized with mouse thyroglobulin (MTg) and evaluated for EAT 28 days later. All β2m -/- mice developed moderate antibodies to MTg, and thyroidal inflammation was comparable to B10.K mice, averaging 35-40%. Spleen cells (SC) from MTg-immunized mice were then injected into syngeneic recipients after stimulation in vitro with MTg or with conserved, thyroxine (T4)- or thyronine (T0)- containing 12mer peptides, hT4(5), hT0(2553), or hT4(2553), derived from the primary hormonogenic sites at position 5 or 2553 of human Tg. As previously shown in another H2(k) strain (CBA/J), all three peptides activated MTg-primed SC to transfer EAT in B10.K mice. hT4(5) and hT4(2553) were further tested in B10.K-Vβ(c) and β2m- B10.K mice. Both peptides expanded thyroiditogenic T cells in either strain, resulting in severe thyroiditis in syngeneic recipients. That EAT can develop in the absence of CD8+ T cells or in the presence of a severely restricted TCR repertoire underscores the remarkable flexibility of the thyroiditogenic T cell profile in the susceptible k haplotype.

Original languageEnglish (US)
Pages (from-to)127-133
Number of pages7
JournalAutoimmunity
Volume27
Issue number3
DOIs
StatePublished - 1998

Keywords

  • EAT
  • Experimental autoimmune thyroiditis
  • T cell repertoire
  • TCR-Vβ(c) mice
  • β2m knockout mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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