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* Department of Microbiology and Immunology, State University of New York, Upstate Medical University, Syracuse, NY 13210; and
Environmental Health Science Center, Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642
Activation of the aryl hydrocarbon receptor (AHR), a basic helix-loop-helix transcription factor, in lymphocytes by the immunosuppressive environmental contaminant 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to cause thymic atrophy in every species studied. We set out to identify the specific hemopoietic cellular populations in which the AHR was activated to lead to thymic atrophy and to determine the effect of AHR activation in those cellular populations. Initially, we examined whether AHR activation in intrathymic dendritic cells could mediate TCDD-induced thymic atrophy. It was found that thymic atrophy occurred only when the AHR could be activated in the thymocytes but not hemopoietic-derived dendritic cells or other APCs. We next analyzed the effect of TCDD on the proliferation of thymocytes in vivo. There was a significant increase in the percentage of thymocytes in the G1 phase of the cell cycle and a significant decrease in the percentage of S plus G2/M thymocytes, especially in the CD4-CD8-CD3- triple-negative intrathymic progenitor cell population 24 h after exposure to 30 µg/kg TCDD. Furthermore, by 12 h after exposure to TCDD, we observed 
60% reduction of 5-bromo-2'-deoxyuridine incorporation in specific intrathymic progenitor cell populations. This reduction persisted for at least 6 days. These data indicate that intrathymic progenitor cells are direct targets of TCDD in the thymus and suggest that TCDD causes thymic atrophy by reducing entrance into cell cycle in these populations.
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