Independent Involvement of CD8⁺CD25⁺Cells and Thyroid Autoantibodies in Disease Severity of Hashimoto's Disease

Abstract

Hashimoto's disease (HD) is well known as an autoimmune thyroid disease caused by the destruction of the thyroid follicles, and can be diagnosed in the subclinical stage with thyroid-specific autoantibodies. However, some patients with HD develop hypothyroidism and are treated with thyroxine (severe HD), but most do not throughout their lives (mild HD). To clarify the immunologic differences between these two groups of patients with HD, we examined serum thyroid autoantibodies (antithyroid peroxidase antibodies and antithyroglobulin antibodies), CD4+ CD25+ cells that contain regulatory T cells and activated helper T cells, and CD8+ CD25+ cells that are activated cytotoxic T cells. There was no significant difference in CD4+ CD25+ cells between these HD groups, although the proportion of CD25+ cells within CD4+ cells increased in both groups as compared to normal controls. The serum titers of the thyroid autoantibodies and the proportion of CD25+ cells within CD8+ cells were higher in patients with severe HD than in those with mild HD. There was no correlation between these two parameters, and a two-dimensional analysis with these parameters differentiated these two groups of patients with HD more clearly. These results indicate that both thyroid autoantibodies and CD8+ CD25+ cells are independently involved in the disease severity of HD and CD4+ CD25+ cells are not related to the severity of HD.

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].…”

Association between the Severity of Hashimoto's Disease and the Functional +874A/T Polymorphism in the Interferon-.GAMMA. Gene

“…Because the +874T allele is associated with high production of IFN-γ [6], which activates cytotoxic T lymphocytes [4], our present findings also suggest that activation of cytotoxic T lymphocytes may be increased in patients with severe HD. Indeed, we previously reported that the proportion of activated cytotoxic T lymphocytes is increased in patients with severe HD [3]. Previous studies have also shown that IFN-γ levels are increased in some patients with HD [8,9] and that intracellular expression of IFN-γ in T cells is increased in HD patients with severely destructed thyroid follicles [10].…”

“…Although there are previous reports that have examined the association of gene polymorphisms with the development of GD and HD [12][13][14], this is the first study showing the significant association of gene polymorphisms with the severity of autoimmune thyroid diseases. We previously reported that activated cytotoxic T lymphocytes and TgAb are independent factors that contribute to the severity of HD and that the proportion of activated cytotoxic T lymphocytes is high in severe HD patients negative for serum TgAb but not in severe HD patients positive for TgAb [3]. These findings are also consistent with our present findings that the frequency of the T allele of IFN-γ was higher in patients with severe HD negative for TgAb but not in patients with severe HD positive for TgAb (Table 3).…”

“…Some patients with GD achieve remission through medical treatment; others do not. The immunologic differences that underlie differences in severity or intractability remain unclear; however, we reported previously that CD8 + CD25 + -activated cytotoxic T lymphocytes and thyroid autoantibodies, especially anti-thyroglobulin antibodies (TgAb), are independently involved in the severity of HD [3]. IFN-γ is a major cytokine produced by type 1 T-helper (Th1) cells, and it activates cytotoxic T lymphocytes, increases cell-mediated cytotoxicity, and suppresses humoral immunity [4].…”

Immune Profile and Signal Transduction of T-Cell Receptor in Autoimmune Thyroid Diseases

“…In HT the Th1 cell response prevails with predominant production of IFN-, IL-2 and TNF- (Fisfalen, Palmer et al, 1997;Fisfalen, Soltani et al, 1997;Watanabe, Yamamoto et al, 2002). The Th2 humoral response pertains to GD with production of cytokines IL-4, IL-5, IL-6, IL-10 and IL-13 and suppression of INF- (Yano, Sone et al, 1995;Abbas Murphy et al, 1996;Fisfalen, Palmer et al, 1997;Fisfalen, Soltani et al, 1997).…”