Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.
NOD.H-2h4 mice, which express I-Ak on the NOD genetic background, spontaneously develop autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies. The incidence of SAT is nearly 100% in mice of both sexes 6-8 weeks after administration of 0.05% NaI in the drinking water. After reaching maximum severity, inflammation is chronic over the next 3-4 months. All mice that develop thyroid lesions also produce MTg-specific IgG1 and IgG2b autoantibodies. Thyroid lesions and anti-MTg autoantibodies did not develop in CBA/J (H-2(k)) or NOD.SWR(H-2(q)) mice after administration of NaI water. Both CD4(+)and CD8(+)T cells are involved in the initial development of SAT. Depletion of CD4(+), but not CD8(+), T cells after thyroid lesions have developed also markedly reduced SAT severity, indicating that CD4(+)T cells are required for both developing and maintaining SAT. Analysis of cytokine gene expression indicated that both Th1 and Th2 cytokines were expressed in thyroids of NOD.H-2h4 mice with SAT. Th1 and proinflammatory cytokines were maximally expressed 4-6 weeks after mice began receiving NaI water, while Th2 cytokine gene expression was greatest at 8-15 weeks, when lesions had reached maximal severity and were in the chronic phase. TGF-beta was highly expressed in NOD.H-2h4 thyroids, irrespective of whether the mice had received NaI water or had thyroid lesions.
Braley-Mullen
H
H
Research Service, Department of Veterans Affairs Medical Center, Columbia, MO, 65212, USA. helen_mullen@muccmail
Sharp
G C
GC
Medling
B
B
Tang
H
H
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006183:H-2 Antigens; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012974:Sodium Iodide / Q000008:administration & dosage; D013954:Thyroglobulin / Q000276:immunology*; D013961:Thyroid Gland / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D016207:Cytokines; D006183:H-2 Antigens; D013954:Thyroglobulin; D012974:Sodium Iodide