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 language | English (US) |
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Pages (from-to) | 127-133 |
Number of pages | 7 |
Journal | Autoimmunity |
Volume | 27 |
Issue number | 3 |
DOIs | |
State | Published - 1998 |
Keywords
- EAT
- Experimental autoimmune thyroiditis
- T cell repertoire
- TCR-Vβ(c) mice
- β2m knockout mice
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology