Apoptosis-induced Decrease of Intrathyroidal CD4 + CD25 + Regulatory T Cells in Autoimmune Thyroid Diseases

Background: We previously showed that the proportion of CD4⁺ T cells was lower and both the proportion and intensity of Fas expression on intrathyroidal CD4⁺ T cells were higher in the thyroid than in the peripheral blood of patients with autoimmune thyroid disease (AITD). Objective: To clarify whether the intrathyroidal CD4⁺CD25⁺ regulatory T (Treg) cells are decreased by Fas-mediated apoptosis in patients with AITD. Design: We examined intrathyroidal and peripheral lymphocytes in 20 patients with AITD (15 patients with Graves' disease and five patients with Hashimoto's disease) and peripheral lymphocytes in 10 healthy volunteers by three-color flow cytometry. Main outcome: The proportion of CD4⁺CD25⁺ cells was lower in the thyroid of patients with AITD than in the peripheral blood of the same patients or the peripheral blood of the healthy subjects. The proportions of CD4⁺CD25⁺CD69⁻ cells and Forkhead box P3 (Foxp3)⁺CD4⁺CD25⁺ cells, which constitute more specific Treg subsets than CD4⁺CD25⁺ cells, were also lower in the thyroid than in the peripheral blood of patients with AITD. The proportion of apoptotic cells was higher among intrathyroidal CD4⁺ cells than among peripheral CD4⁺ cells and higher among intrathyroidal CD4⁺CD25⁺ cells than among intrathyroidal CD4⁺CD25⁻ cells. Conclusion: These results indicate that intrathyroidal Treg cells are decreased in response to apoptosis in patients with AITD. This decrease in Treg cells may contribute to the incomplete regulation of autoreactive T cells in AITD.