2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a prevalent environmental toxicant that may pose serious human health concerns. It is considered as the most potent toxic compound of the halogenated aromatic hydrocarbons. Among its many toxic effects, TCDD causes tremendous injury to the immune system, which is manifested by marked thymic atrophy and peripheral lymphocyte dysfunction. Despite extensive studies, the exact mechanism for TCDD immunotoxicity remains unknown. Recent studies from our laboratory have demonstrated that TCDD can increase the levels of apoptosis in the thymus. In the current study, we hypothesize that TCDD exerts its immunotoxic effects on fetal thymocytes by dysregulation of FasL-based apoptosis. To test this hypothesis, prenatal studies will be conducted in Fas-deficient and FasL-defective animal models. The successful completion of these studies will provide novel information on the mechanisms by which TCDD may alter T cell education in the fetal thymus leading to increased susceptibility to autoimmune diseases and cancer during adulthood.
