Ontogenic development of murine fetal thymocytes is accelerated by 3,3′,4,4′-tetrachlorobiphenyl

Abstract

Polychlorinated hydrocarbons such as biphenyls or dioxins interfere with cellular processes by gene induction via ligand-activated binding of the cytosolic Ah-receptor to specific DNA elements. The thymus is a target organ for these processes and immunosuppression a hallmark of polychlorinated hydrocarbon toxicity. Using flow cytometry we analysed the development of thymocytes in fetal thymus organ cultures (FTOC) exposed to tetrachlorobiphenyl (TCB) for up to one week. We show that exposure to TCB changes the normal developmental pathways of fetal thymocytes within days. Overall fewer thymocytes are found in TCB-treated cultures from day 4 on, and significantly more CD8 positive thymocytes are detectable. These cells express the T-cell receptor, but not heat-stable antigen or IL2-receptor, giving them a mature phenotype. Moreover, relatively more CD4/CD8 double-negative thymocytes express CD44, a molecule involved in lymphocyte-epithelial interaction. We suggest that, at least for the CD8 single-positive thymocyte population, maturation is accelerated, and this may be due to TCB interference with physiological thymocyte-epithelial interactions.