We aimed to establish and extend the characterization of murine models of thyroiditis and Graves' ophthalmopathy (GO), induced by transfer of TSH receptor (TSHR) primed T cells.

Experiments were performed in a different animal unit but using female BALB/cbyJico mice from the same supplier as previously. We report our findings together with a re-evaluation of the earlier studies.

In the first experiment, genetic immunization (GI) or TSHR fusion protein (FP) induced TSHR antibodies in all 9 mice. Some of the antibodies functioned as TSAB and/or TBII with 2/7 mice having elevated T4. Thyroiditis and orbital changes were absent. Splenocyte transfer induced no immune response in naïve BALB/cbyJico recipients.

Subsequently GI or FP treated mice were maintained in either 'local' or 'Brussels' conditions (water, chow and bedding). TSHR antibodies were induced in 9/9 'Brussels' (with decreased T4 in 1/9) but 5/9 'local' mice. No thyroiditis or orbital changes were induced but misleading fixation artifacts in extra-ocular muscles were noted. Non-specific in vitro stimulation induced more CD-4+/IL-4+ cells in 'Brussels' maintained. TSHR stimulation produced a significant increase in IL-4 secretion in 6/9 'local' but 1/7 'Brussels' mice.

Thyroids from many TSHR treated and control mice contained ectopic thymus.

Our results confirm that thyroiditis is required for disease transfer but indicate the heterogeneity in TSHR induced immune response in an inbred strain. Ectopic thymus can masquerade as thyroiditis and care is required to avoid muscle artifacts. Since neither animal unit is pathogen free, microbial environment may contribute to determining TSHR induced responses.