de Heer C, van Driesten G, Schuurman H J, Rozing J, van Loveren H
Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Toxicology. 1995 Dec 10;103(3):195-203. doi: 10.1016/0300-483x(95)03135-3.
Tolerance to minor lymphocyte stimulatory-1a (Mls-1a) antigens is associated with clonal deletion of cells carrying the T cell receptor variable region V beta 6. Thymic epithelial cells may contribute to the intrathymic negative selection of potentially autoreactive V beta 6+ cells. Because 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts on thymic epithelial cells, we hypothesized that it may interfere with intrathymic selection processes. In the present study, this was addressed by exposing Mls-1a DBA/2 mice to a single thymotoxic dose of TCDD. The emergence of V beta 6+ cells in thymus, spleen, and mesenteric lymph nodes was investigated during the subsequent recovery of TCDD-induced thymic atrophy. In addition, the extrathymic differentiation of T lymphocytes in the liver was studied. TCDD exposure resulted in a severe thymic atrophy, and an increase in hepatic mononuclear cells. However, we were not able to demonstrate any emergence of potentially autoreactive mature V beta 6+ T cells, that differentiated either intrathymically or extrathymically, in TCDD-exposed DBA/2 mice.