Effects of TCDD on the fate of naive dendritic cells

The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes immune suppression via activation of the aryl hydrocarbon receptor. Dendritic cells (DCs), the professional antigen-presenting cells in the immune system, are adversely affected by TCDD. We hypothesized that TCDD alters DC homeostasis, resulting in a loss of DCs in naive mice. To test this hypothesis, C57Bl/6 mice were gavaged with either vehicle or an immunosuppressive dose of TCDD (15 μg/kg). TCDD exposure decreased the frequency and number of splenic CD11c^high DCs on day 7 when compared with vehicle-treated controls. TCDD increased the expression of CD86 and CD54, while decreasing the frequency of splenic CD11c^high DCs expressing CD11a and major histocompatibility complex (MHC) class II. Moreover, TCDD selectively decreased the CD11c^highCD8α2^-33D11⁺ splenic DCs specialized at activating CD4¹ T cells but did not affect the regulatory CD11c^highCD8α¹DEC205¹ splenic DCs. TCDD did not alter the number or frequency of CD11c^low splenic DCs but decreased their MHC class II and CD11a expression. Loss of splenic CD11c^high DCs was independent of Fas-mediated apoptosis and was not due to alterations in the numbers of common DC precursors in the bone marrow or their ability to generate steady-state DCs in vitro. Instead, increased CCR7 expression on CD11c^high DCs suggested involvement of a migratory event. Popliteal and brachial lymph node CD11c¹ cells showed elevated levels of MHC class II and CD40 following TCDD exposure. Collectively, this study shows the presence of a TCDD-sensitive splenic DC subpopulation in naive mice, suggesting that TCDD may induce suppression of T-cell-mediated immunity by disrupting DC homeostasis.