Flexibility of the Thyroiditogenic T Cell Repertoire for Murine Autoimmune Thyroiditis in CD8-Deficient (B2m -/-) and T Cell Receptor VBC Congenic Mice

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 H2k strain. To further test this flexibility, congenic B10.K mice lacking CD8+ T cells (B2m -/-) or harboring 70% T cell receptor (TCR) V6 gene deletions (V6C) were immunized with mouse thyroglobulin (MTg) and evaluated for EAT 28 days later. All 62m -/- 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 (TO)- 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 H2k 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-V6C and ß2m- 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.