Role of Fas mediated apoptosis in the process of autoimmune thyroid diseases : possible involvement of Fas ligand (FasL) expression in breakdown of "immunoprevileged site" formation

点击翻译按钮获取中文摘要

Fas ligand (FasL) is expressed in thyrocytes, and appear to plays an important role to make normal thyroid tissue to be "immunoprevileged site." Since IL-1β is strongly expressed in Graves' thyroid tissue, we tried to determine the possible involvement of IL-1β in the process of Graves' disease regarding Fas/FasL interaction between thyrocytes and T cells.Immunohistochemical analysis has shown that the percentage of FasL-positive thyrocytes in Graves' thyroids was less than in normal thyroids. In contrast, many thyrocytes in Graves' disease expressed Fas molecule. Treatment of thyrocytes with IL-1β in vitro increased Fas expression but markedly reduced FasL expression. Activated T cells in vitro, which strongly expressed FasL, induced Fas-mediated apoptosis in IL-1β stimulated thyrocytes.Massive CD4^+ T cell infiltration has been demonstrated in Graves' thyroid tissue. Western blotting analysis revealed that FasL expression of thyroid infiltrating CD4^+ T cells was significantly intense than that of peripheral blood (PB) CD4^+ T cells. Although the cytotoxic activity of PB CD4^+ T cells toward IL-1β stimulated thyrocytes was very week, thyroid infiltrating CD4^+ T cells of Graves' disease apparently induced Fas mediated apoptosis toward IL-1β stimulated thyrocytes. Fas expression was also markedly increased in thyroid-infiltrating CD4^+ T cells, however, the cells were resistant to Fas-mediated apoptosis, probably due to the increased expression of Bcl-x2.Previous studies have shown that IL-1β increases the expression of adhesion molecules and stimulates the migration of activated T cells from peripheral blood into thyroid tissues. In addition, our present results indicate that IL-1β increases the sensitivity of Fas mediated apoptosis of thyrocytes induced by CD4^+ T cells, which may attribute to the breakdown of "immunoprevileged site" formation in thyroid tissues of Graves' disease.