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 autoimmu ne thyroiditis (SAT) development, and anti-thyroglobulin autoantibody level s correlate with SAT severity. Immunohistochemical staining of thyroids obt ained 2-10 weeks after administration of NaI water suggested that CD4+ T ce lls initially infiltrated the thyroid, followed by CD8+ T cells and B cells . Intrathyroidal CD4+ T cells are more numerous than CD8+ T cells. CD4+ T c ells and B cells form aggregates in the thyroid, while CD8+ T cells are sca ttered throughout the thyroid. Intrathyroidal germinal centre-like structur es could be observed in thyroid lesions with 2-3+ SAT and intrathyroidal B cells co-expressed OX40L. By RT-PCR, intrathyroidal expression of OX40L, OX 40, CD40L, IL-2R CTLA-4 and Ig beta mRNA correlated closely with the SAT se verity score. These molecules were not expressed in normal thyroids. In the spleen, OX40L-positive cells were detected at 2 weeks and increased 4-6 we eks after NaI water. OX40, OX40L, CD40L, IL-2R and B7-1 as well. as IFN-gam ma 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 N aI water. These results suggest that in NOD.H-2h4 mice, the OX40L, OX40, CD 40L and B7 molecules, which increase in the spleen and thyroid of these mic e after receiving NaI water, may play a role in SAT development, implying t hat one or more of these molecules might be good targets for the prevention or treatment of SAT. (C) 2001 Academic Press.