Development of a murine model of autoimmune thyroiditis induced with homologous mouse thyroid peroxidase

Autoimmune thyroid disease ( AITD) is a common autoimmune disease. Thyroid peroxidase ( TPO) is a well characterized autoantigen in AITD. Autoantibodies and autoreactive T lymphocytes to TPO are believed to play a major role in the pathogenesis of lymphocytic thyroiditis. To understand the pathogenic mechanisms of AITD and the role of TPO, we have established a mouse model of lymphocytic thyroiditis by immunizing C57Bl/ 6 ( H- 2(b)), CBA ( H- 2(k)), and C57Bl/ 6 x CBA F1 mice with recombinant murine TPO ( rmTPO) ectodomain comprising amino acid residue 1 - 837 produced in Escherichia coli. Mice were immunized with 30 mu g purified ectodomain in complete Freund's adjuvant. Antibodies against rmTPO were detected in the serum of all mice from day 21 onward. Draining lymph node cells from rmTPO- immunized animals showed dose- dependent proliferation to TPO stimulation. Mice killed at d 50 and 90 revealed variable degrees of thyroiditis with infiltration of mononuclear cells and destruction of thyroid follicles. C57Bl/ 6 and the F1 mice, in comparison with CBA mice, showed a greater degree of thyroiditis. There was a lack of correction between the intensity of thyroiditis and the anti-TPO response. Immunotyping of the thyroid cellular infiltrates showed predominantly CD4(+) T cells and B220(+) B cells but scanty CD8(+) T cells. None of the control mice injected with the purified fusion partner developed anti- TPO antibodies and thyroiditis. In conclusion, a genuine autoimmune mouse model of lymphocytic thyroiditis was established using autologous mouse TPO. This new model induced with autologous TPO will lead to a better understanding of the mechanisms in destructive thyroiditis and will assist in the development of new strategies for modulating the pathogenic immune response.