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.

Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis.

“…Such a trend was also found in the control group but the correlation was not statistically significant, probably due to the small number of subjects. Similar findings were reported by Maruoka et al in euthyroid patients with AITD and healthy subjects (32). It appears that more cells express Fas with age and this may become more prominent in HT, a condition associated with a higher degree of apoptosis in relation to GD.…”

“…However, the lack of FasL expression by the same cells may prevent their elimination by apoptotic death. In this regard, a previous study also reported an increased proportion of Fas-expressing CD4 cells in untreated GD while expression of FasL was not detected (32).…”

Ratio of Serum IgG3 to Total IgG Concentration and Goiter Size Are Independent Factors in Intractability of Graves' Disease

“…Immune differences that underlie differences in the severity and intractability of these diseases remain unclear, and disease severity and intractability are difficult to predict. However, we have shown that particular lymphocyte subsets [4][5][6][7] and serum soluble CD8 [8] are related to the severity and intractability of these diseases. The levels of TSH receptor antibody (TRAb), IL-4, and IgE are also reported as the factors involved in the prediction of remission in GD [9,10].…”

Decrease of Intrathyroidal CD161+V.ALPHA.24+V.BETA.11+ NKT Cells in Graves' disease

“…Two typical AITDs are Hashimoto's disease (HD) and Graves' disease (GD), and with either of these diseases the lymphocytes infiltrate the thyroid of patients [1][2][3][4]. We previously reported differences between the proportions of particular lymphocyte subsets in the thyroid and peripheral blood and suggested involvement of these subsets in the pathogenesis of AITD [5][6][7][8][9][10]. We have also reported the association between the polymorphism of interferon-γ gene and the severity of HD [11].…”