ALTERNATE IMMUNE-SYSTEM TARGETS FOR TCDD - LYMPHOCYTE STEM-CELLS AND EXTRATHYMIC T-CELL DEVELOPMENT

We here summarize evidence that thymic atrophy induced by 2,3,7,8-tetr achlorodibenzo-p-dioxin (TCDD) can be mediated, at least in part, by d amage to extrathymic T-cell precursors in bone marrow and fetal liver. This atrophy induction does not involve apoptotic mechanisms in thymo cytes affected by the bcl-2 proto-oncogene. TCDD mediates atrophy indu ction through its specific receptor (the AhR) and not through effects on the estrogen receptor. Both TCDD and estradiol induce extrathymic T -cell differentiation in the liver. These extrathymic T-cell populatio ns include cells expressing elevated levels of V beta T-cell receptors that are normally deleted in thymic development.