Vβ8.2 transgene expression interferes with development of experimental autoimmune thyroiditis in CBA k/q but not k/k mice

The thyroiditogenic T cell receptor (TCR) repertoire is not yet well defined in murine experimental autoimmune thyroiditis (EAT). Our recent work has shown that, while Vβ8⁺ T cells have no major role in EAT induction with mouse thyroglobulin (MTg), Vβ13 may be involved. To examine the effect of skewing the TCR repertoire on EAT development, CBA (H2(k)) mice were mated with B1O.Q mice harboring an ovalbumin-specific Vβ8.2⁺ TCR transgene (trg), and the trg⁺ mice were backcrossed to CBA. FAGS analysis showed that peripheral blood T cells from trg⁺ mice had about 76 and 90% Vβ8.2⁺ cells in the CD4⁺ and CD8⁺ subsets, respectively, compared with about 15 and 11% in trg^- sibs. The transgenic CBA k/k and k/q mice were immunized with MTg and sacrificed 28 days later. In all trg⁺ mice, anti-MTg titers and T cell proliferative responses to MTg were significantly lowered. However, thyroid infiltration was distinctly different in the two strains of transgenic mice; a significant decrease was seen primarily in k/k, but not k/k, trg⁺ mice. Thus, skewing the TCR repertoire to overexpress an irrelevant TCR revealed the possession of a less flexible thyroiditogenic TCR repertoire in k/q, but not k/k, mice.