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-tetrachlorodibenzo-p-dioxin (TCDD) can be mediated, at least in part, by damage to extrathymic T-cell precursors in bone marrow and fetal liver. This atrophy induction does not involve apoptotic mechanisms in thymocytes affected by the bcl-2 proto-oncogene. TCDD mediates atrophy induction 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 populations include cells expressing elevated levels of V beta T-cell receptors that are normally deleted in thymic development.
Silverstone
A E
AE
Department of Microbiology and Immunology, State University of New York Health Science Center, Syracuse 13210-2375.
Frazier
D E
DE
Gasiewicz
T A
TA
D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000633:toxicity; D004958:Estradiol / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D000090063:Proto-Oncogene Mas; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D011959:Receptors, Estradiol / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
C000715470:MAS1 protein, human; D000072317:Polychlorinated Dibenzodioxins; D000090063:Proto-Oncogene Mas; D018336:Receptors, Aryl Hydrocarbon; D011959:Receptors, Estradiol; D004958:Estradiol; D003907:Dexamethasone