Increased Intensities of Fas Expression on Peripheral T-Cell Subsets in Severe Autoimmune Thyroid Disease

Abstract

Fas (CD95)-Fas ligand (FasL; CD178)-induced apoptosis is necessary for the maintenance of self-tolerance. To clarify whether or not any abnormalities in the Fas-FasL system exist in patients with autoimmune thyroid disease (AITD), we examined the expression of Fas and FasL on peripheral T lymphocytes by three-color flow cytometry in 113 patients with AITD and 49 healthy controls. The intensities of Fas expression in both CD4⁺ and CD8⁺ T cells decreased in thyrotoxic patients with Graves' disease (GD), but increased in both patients with severe Hashimoto's disease (HD) undergoing treatment and seriously intractable patients with GD continuously positive for thyrotropin (TSH) receptor antibody despite treatment with antithyroid drugs for more than 5 years. The proportion of Fas expression was increased in CD4⁺ T cells from patients with untreated GD, and in CD8⁺ T cells from patients with severe HD. The proportion of CD8⁺ T cells decreased in patients with severe HD. FasL were not expressed on T cells in controls and patients with AITD. These results indicate that (1) the intensities of Fas expression on peripheral T cells increase in severe autoimmune thyroid diseases and (2) both the intensity and the proportion of Fas expression may be important for the induction of apoptosis.