Depletion of CD4 + CD25 + regulatory T cells exacerbates sodium iodide‐induced experimental autoimmune thyroiditis in human leucocyte antigen DR3 (DRB1*0301) transgenic class II‐knock‐out non‐obese diabetic mice

Summary Both genetic and environmental factors contribute to autoimmune disease development. Previously, we evaluated genetic factors in a humanized mouse model of Hashimoto's thyroiditis (HT) by immunizing human leucocyte antigen DR3 (HLA‐DR3) and HLA‐DQ8 transgenic class II‐knock‐out non‐obese diabetic (NOD) mice. DR3 + mice were susceptible to experimental autoimmune thyroiditis (EAT) induction by both mouse thyroglobulin (mTg) and human (h) Tg, while DQ8 + mice were weakly susceptible only to hTg. As one environmental factor associated with HT and tested in non‐transgenic models is increased sodium iodide (NaI) intake, we examined the susceptibility of DR3 + and/or DQ8 + mice to NaI‐induced disease. Mice were treated for 8 weeks with NaI in the drinking water. At 0·05% NaI, 23% of DR3 + , 0% of DQ8 + and 20% of DR3 + DQ8 + mice had thyroid destruction. No spleen cell proliferation to mTg was observed. Most mice had undetectable anti‐mTg antibodies, but those with low antibody levels usually had thyroiditis. At 0·3% NaI, a higher percentage of DR3 + and DR3 + DQ8 + mice developed destructive thyroiditis, but it was not statistically significant. However, when DR3 + mice had been depleted of CD4 + CD25 + regulatory T cells prior to NaI treatment, destructive thyroiditis (68%) and serum anti‐mTg antibodies were exacerbated further. The presence of DQ8 molecules does not alter the susceptibility of DR3 + DQ8 + mice to NaI‐induced thyroiditis, similar to earlier findings with mTg‐induced EAT. Susceptibility of DR3 + mice to NaI‐induced EAT, in both the presence and absence of regulatory T cells, demonstrates the usefulness of HLA class II transgenic mice in evaluating the roles of environmental factors and immune dysregulation in autoimmune thyroid disease.