Characteristics of inflammatory cells in spontaneous autoimmune thyroiditis of NOD.H-2h4 mice.
Thyroid lesions develop in most NOD.H-2h4 mice 6 weeks after they are given 0.05% NaI in drinking water. B cells are required for spontaneous autoimmune thyroiditis (SAT) development, and anti-thyroglobulin autoantibody levels correlate with SAT severity. Immunohistochemical staining of thyroids obtained 2-10 weeks after administration of NaI water suggested that CD4+ T cells initially infiltrated the thryoid, followed by CD8+ T cells and B cells. Intrathyroidal CD4+ T cells are more numerous than CD8+ T cells. CD4+ T cells and B cells form aggregates in the thyroid, while CD8+ T cells are scattered throughout the thyroid. Intrathyroidal germinal centre-like structures could be observed in thyroid lesions with 2-3+ SAT and intrathyroidal B cells co-expressed OX40L. By RT-PCR, intrathyroidal expression of OX40L, OX40, CD40L, IL-2R, CTLA-4 and Igbeta mRNA correlated closely with the SAT severity score. These molecules were not expressed in normal thyroids. In the spleen, OX40L-positive cells were detected at 2 weeks and increased 4-6 weeks after NaI water. OX40, OX40L, CD40L, IL-2R and B7-1 as well as IFN-gamma and IL-4 mRNA were minimally expressed in normal spleens, usually began to be expressed at 2 weeks and increased to maximal level 4-8 weeks after NaI water. These results suggest that in NOD.H-2h4 mice, the OX40L, OX40, CD40L and B7 molecules, which increase in the spleen and thyroid of these mice after receiving NaI water, may play a role in SAT development, implying that one or more of these molecules might be good targets for the prevention or treatment of SAT.
Yu
S
S
Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65212, USA.
Medling
B
B
Yagita
H
H
Braley-Mullen
H
H
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D023201:CD40 Ligand / Q000235:genetics; D060908:CTLA-4 Antigen; D015870:Gene Expression; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D053278:OX40 Ligand; D012333:RNA, Messenger; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012974:Sodium Iodide / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics; D048069:Tumor Necrosis Factors; D014867:Water
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D012333:RNA, Messenger; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors; D014867:Water; D023201:CD40 Ligand; D000069594:Abatacept; D012974:Sodium Iodide