Role of MHC class I expression and CD8(+) T cells in the evolution of iodine-induced thyroiditis in NOD-H2(h4) and NOD mice.
Dietary iodine has long been known to influence the development of human autoimmune thyroid disease. In nonobese diabetic (NOD) and NOD-H2(h4) mice elevated dietary iodine has been shown to induce autoimmune thyroid disease. Immune responses to thyroid antigens can be detected in these mouse strains, including T cell responses in the NOD-H2(h4) mouse to thyroid peroxidase. Cell transfer studies and antibody depletion experiments reveal a requirement for both CD4(+) T cells and CD8(+) T cells in the development of thyroid autoimmunity. Histological analyses of the thyroids show that following 1 week of iodine administration MHC class I expression is elevated on thyroid follicular cells and CD4(+) and CD8(+) T cells have begun to infiltrate the gland. Although MHC class II expression on thyroid epithelial cells was also elevated, the tempo of expression was slower and the extent of expression was far less than that for MHC class I. Depletion of CD8(+) T cells at early stages of disease induction inhibited not only thyroid infiltration and autoantibody production but also reduced the levels of MHC expression in the thyroid, suggesting that cytokine production by infiltrating lymphocytes was responsible for the increased MHC expression.
Verma
S
S
Department of Pathology, University of Cambridge, Cambridge, GB.
Hutchings
P
P
Guo
J
J
McLachlan
S
S
Rapoport
B
B
Cooke
A
A
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000276:immunology; D007455:Iodine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D001323:Autoantibodies; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D013954:Thyroglobulin; D007455:Iodine; D007453:Iodide Peroxidase