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

Exp Clin Immunogenet. 1994;11(2-3):75-85. doi: 10.1159/000424196.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / drug effects*
  • Cell Differentiation / drug effects
  • Flow Cytometry
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Polychlorinated Biphenyls / pharmacology*
  • Receptors, Aryl Hydrocarbon / metabolism
  • T-Lymphocyte Subsets / drug effects
  • Thymus Gland / cytology
  • Thymus Gland / drug effects*

Substances

  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Biphenyls
  • 3,4,3',4'-tetrachlorobiphenyl