Proliferation inhibition and CD4/CD8 thymocyte subset skewing by in vivo exposure of C57BL/6 mice to Ah receptor-binding 3,3',4,4'-tetrachlorobiphenyl.
3,3',4,4'-Tetrachlorobiphenyl (TCB) and other Ah receptor-binding xenobiotics lead to thymus atrophy and immunosuppression, the former possibly causing the latter. In order to better understand the TCB-induced events in the murine thymus, we analyzed the effects of TCB on the proliferation capacity and maturation kinetics of different thymocyte subsets in 2-week-old C57BL/6 mice (i.e. of the Ahb-1 'dioxin-sensitive' genotype). Mice were injected with a single dose of TCB, and the development of thymocytes was followed up for 10 days using flow cytometric surface marker analysis combined with measurement of DNA content by 7-amino-actinomycin D staining. Already 2 days after exposure to TCB, fewer of the more immature thymocytes (CD4-CD8-, CD4-CD8+ alpha beta TCR-) were proliferating than in thymi from control animals. Eventually this led to a severe decrease in thymus cellularity. Moreover, a shift towards the CD4-CD8+ mature subpopulation was observed. The effects were reversible, and proliferation and CD4/CD8 subset distribution returned to normal levels within the observation period. The results are in good agreement with the data obtained previously in vitro with fetal thymus organ cultures.
Esser
C
C
Medical Institute of Environmental Hygiene, Düsseldorf, Germany.
Lai
Z
Z
Gleichmann
E
E
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl