Experimental murine thyroiditis induced by porcine thyroid peroxidase and its transfer by the antigen-specific T cell line

Abstract

Thyroid peroxidase purified from porcine thyroid (pTPO) was found to induce an experimental murine thyroiditis with genetic restriction which was very different from that induced by mouse thyroglobulin (mTg). C57BL/6 and C57BL/10 (both H-2b) were good responders for thyroiditis, whereas A/J (H-2a), BALB/c (H-2d), DBA/2 (H-2d), CBA (H-2k), C3H/He (H-2k), and SJL/J (H-2s) were poor responders. Genetic analyses using congenic or recombinant strains revealed the following results: The H-2-linked gene (probably the I-A subregion) had a weak association with the induction of thyroiditis, and at least one non-H-2-linked gene controlled the development of thyroid lesions; antibody production to pTPO, porcine thyroglobulin (pTg) and mTg did not correlate with the incidence of thyroiditis in any strain. None of the murine thyroid microsome-specific antibodies tested by the indirect immunofluorescent technique was detected. The T cell line specific for pTPO was successfully transferred to produce thyroid lesions in C57BL/6 mice. Thyroiditis appeared 3 days after the transfer of T cell blasts, and a low concentration of anti-pTPO antibodies was detected concurrently. Thyroid lesions remained up to 48 days with almost the same extent of thyroiditis, but anti-pTPO antibodies gradually increased. In the vaccination experiments using either 0.645 C/kg (2500 rad)-irradiated or 0.3% glutaraldehyde-fixed T cell blasts, the induction of thyroid lesions by transfer was strongly suppressed. Glutaraldehyde fixation was more effective than X-irradiation in preventing thyroiditis after the transfer of T cell blasts. Vaccination also suppressed significantly the development of thyroid lesions after pTPO administration.