2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol affect thymocytes at different stages of development in fetal thymus organ culture

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and estrogen induce thymic atrophy and alter thymocyte development. In the present study we investigate whether TCDD and the synthetic estrogen diethylstilbestrol (DES) alter intrathymic development by the same or different mechanisms. We compared the effects of TCDD and DES on thymocyte development in fetal thymus organ culture (FTOC) and found that both compounds caused a reduction in cell yield. TCDD-and DES-treated FTOCs yielded fewer CD4+CD8+ double-positive cells. However TCDD treatment also led to a greater percentage of cells in the CD8+ single-positive compartment. At lower dioxin concentrations, our results demonstrated an actual increase in CD8+ cells, whereas DES-treated fetal thymocytes were mainly enriched in CD4-CD8- double-negative cells. More alpha beta-TCR+ positive cells were seen in TCDD-but not in DES-exposed cultures. Furthermore, in this study we found that TCDD and DES also alter intrathymic development at different stages in the CD4-CD8- double-negative compartment. TCDD induced a relative increase in c-kit+CD44+CD25-HSA-thymocytes, while DES induced an relative increase in c-kit-CD44-CD25+HSA+ cells. RT-PCR revealed that TCDD reduced RAG-1, RAG-2 and TdT gene expression in the CD4-CD8- double-negative thymocytes, Go-treatment by TCDD and DES in FTOC yielded a mixture of effects induced by each agent. Taken together, our results demonstrate that TCDD and DES affect thymocytes at different stages of development, suggesting distinct mechanisms for induction of thymic atrophy. (C) 1998 Academic Press.