| Research Abstract |
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.
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