Reduction in the Suppressor-Inducer T Cell Subset and Increase in the Helper T Cell Subset in Thyroid Tissue from Patients with Graves' Disease

Abstract

The expression of surface markers associated with activation and characterization was compared among T cells in thyroid glands and peripheral blood of 10 patients with Graves' hyperthyroidism receiving chronic antithyroid drug therapy, in peripheral blood of 15 patients with untreated hyperthyroid Graves' disease, and in peripheral blood of 21 normal subjects using two-color flow cytometry. In the chronically treated Graves' disease patients, the percentage of activated T cells (HLA-DR+ T cells) among total T cells was significantly higher in thyroid tissue than in peripheral blood, and the increase in percent activated T cells was also significant among both helper/inducer T cell (CD4+ cell) and suppressor/cytotoxic T cell (CD8+ cell) subsets. The percentage of activated T cells in peripheral blood was not significantly different between chronically treated hyperthyroid Graves' patients and normal subjects, whereas the percentage of activated T cells in the peripheral blood from untreated hyperthyroid Graves' disease patients was significantly higher than that in normal subjects or chronically treated hyperthyroid Graves' patients. The percentages of CD4+ cells and CD8+ cells among total T cells were not different between thyroid tissues and peripheral blood in patients with chronically treated hyperthyroid Graves' disease. When CD4+ were further divided into helper T cells (CD4+2H4- cells) and suppressor-inducer T cells (CD4+2H4+ cells) using two-color flow cytometry, the percentage of helper T cells among CD4+ cells was significantly higher in thyroid tissue than in peripheral blood, resulting in an increased ratio of CD4+2H4- cells to CD4+2H4+ cells. The percentage of CD4+2H4+ cells in peripheral blood, however, was not significantly different among untreated and chronically treated Graves' disease patients and normal subjects. From the findings of abnormalities in intrathyroidal T cell subsets, we suggest that the decrease in the function of suppressor T cells within the thyroids of Graves' disease patients may be due to a decrease in CD4+2H4+ cells within thyroid tissue.

CD4+ T Cell-Mediated Cytotoxicity Toward Thyrocytes: The Importance of Fas/Fas Ligand Interaction Inducing Apoptosis of Thyrocytes and the Inhibitory Effect of Thyroid-Stimulating Hormone

“…The accumulation of activated CD4 ϩ T cells in thyroid gland from patients with Graves' disease has been demonstrated (Ishikawa et al, 1987;Ishikawa et al, 1993), and restricted T cell receptor gene usage was recently demonstrated in thyroidal infiltrate from Graves' patients (Davies et al, 1991a;1991b). These data suggest that Ag-specific T cell activation is present in thyroid glands from Graves' patients.…”

“…In vitro studies have also shown that thyrocytes function as stimulatory APCs to T cells (Eguchi et al, 1995;Eguchi et al, 1988;Matsuoka et al, 1996;Nagataki and Eguchi, 1992), suggesting the presence of antigen (Ag)-dependent active cellular interactions between thyrocytes and T cells in thyroid glands of patients with Graves' disease. Activated CD4 ϩ T cells have been found in thyroid glands of patients with Graves' disease (Eguchi, et al, 1995;Eguchi et al, 1988;Ishikawa et al, 1987;Ishikawa et al, 1993;Nagataki and Eguchi, 1992). Results of in vitro studies have shown that activated CD4 ϩ T cell clone express Fas ligand (FasL) and kill Fas ϩ target cells (Ju et al, 1994;Rouvier et al, 1993;Stalder et al, 1994).…”

Circulating Activated T Lymphocyte Subsets in Patients with Silent Thyroiditis.

“…In contrast, the percentage of circulating CD8+ cells was lower and that of HLA-DR+ cells was higher in patients with Graves' disease than those in normal controls [12][13][14]. Since then, the percentage of activated T cell subsets in patients with autoimmune thyroid diseases has been reported, using two-color dye labeling and dual laser activated cell sorter analysis [15][16][17][18].…”

“…The activated T cells in various types of autoimmune diseases, KUSHIMA et al including Graves' disease, have been measured with monoclonal antibodies to the surface antigens of T cells [141. A few years later, the percentage of peripheral blood activated T cell subsets in patients with autoimmune thyroid diseases, measured by two-color dye labelling and dual laser flow cytometry, were reported [15][16][17][18]. In the majority of the former reports on thyroid diseases such as Graves' disease and Hashimoto's thyroiditis, the percentages of all activated matured T (HLA-DR+CD3+), activated helper/inducer T (HLA-DR+CD4+), and activated suppressor/cytotoxic T (HLA-DR+CD8+) cells in the peripheral blood were higher than those of healthy volunteers, but the results were conflicting because of differences in methods and subjects.…”

Accumulation of Identical T Cell Clones in the Right and Left Lobes of the Thyroid Gland in Patients with Graves' Disease. Analysis of T Cell Clonotype in vivo.

“…These T cells are mainly CD4+ memory cells [9][10][11] . On the other hand, thyroid follicular cells in GD patients aberrantly express HLA class II molecules and present antigens [12].…”