Thymic stroma exposed to arylhydrocarbon receptor-binding xenobiotics fails to support proliferation of early thymocytes but induces differentiation.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 3,3',4,4'-tetrachlorobiphenyl (TCB), two ubiquitous environmental pollutants, accelerate thymocyte maturation, and eventually lead to thymus atrophy. These processes are mediated by binding of TCDD or TCB to the cytosolic arylhydrocarbon receptor (AhR) abundant in the thymus, which acts as a ligand-activated transcription factor. At several stages of their maturation thymocytes need the interaction with thymus stroma. We tested whether thymocytes themselves or the thymus stroma are targets of AhR-binding compounds for interference with thymocyte maturation. We depleted fetal thymus lobes from proliferating cells, i.e., thymocytes, by treatment with deoxyguanosine and recultivated them with immature thymocytes (CD4-CD8-), exposing either the stroma or the thymocytes to TCDD or TCB before recultivation. Although CD4-CD8- immature thymocytes could differentiate in TCB-treated stroma, expansion of the cells was severely impaired. Selective exposure of thymocytes to AhR-binding compounds likewise did not impair the capacity of differentiation of CD4-CD8- thymocytes. These cells, however, could expand when transferred into new lobes that had not been exposed to TCDD or TCB. TCB treatment of fetal thymi leads to an accumulation of phenotypically mature CD4-CD8+ cells. We show here that these cells do not belong to the transient CD4-CD8+ thymocytes, as previously suggested, because in recultivation experiments they do not give rise to any thymocyte subset further down the maturation pathway.
Kremer
J
J
Division of Immunology, Medical Institute for Environmental Hygiene, Heinrich Heine University of Düsseldorf, Germany.
Gleichmann
E
E
Esser
C
C
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000166:cytology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009924:Organ Culture Techniques; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000196:embryology
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl