THYMIC ALTERATIONS INDUCED BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ARESTRICTLY DEPENDENT ON ARYL-HYDROCARBON RECEPTOR ACTIVATION IN HEMATOPOIETIC-CELLS

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related congeners affec t the immune system, causing immunosuppression and thymic atrophy in a variety of animal species, TCDD is believed to exert its effects prim arily through the ligand-activated transcription factor, the aryl hydr ocarbon receptor (AhR). Although the AhR is found at high levels in bo th thymocytes and thymic stroma, it is uncertain in which cells TCDD i s activating the AhR to cause alterations in the thymus, Some investig ators have suggested that stromal elements, primarily epithelial cells , within the thymus are the primary targets for TCDD. Others have sugg ested that atrophy is due to a direct effect on thymocytes, either by apoptosis or by altering the development of progenitor cells, By produ cing chimeric mice with TCDD-responsive (AhR(+/+)) stromal components and TCDD-unresponsive (AhR(-/-)) hemopoietic components. or the revers e, we have clarified the role of stromal vs hemopoietic elements in TC DD-induced thymic alterations, Our results show that the targets for T CDD-induced thymic atrophy and phenotypic alterations are strictly in the hemopoietic compartment and that TCDD activation of epithelial cel ls in the stroma is not required for thymic alterations. Furthermore, changes observed in the putative stem cell populations of these chimer ic mice are also dependent on TCDD activation of the AhR in hemopoieti c elements.