2,3,7,8-Tetrachlorodibenzo-p-dioxin affects the number and function of murine splenic dendritic cells and their expression of accessory molecules

Primary T cell-mediated immune responses are highly susceptible to suppress ion by 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) exposure, yet direct eff ects of TCDD on T cells have been difficult to demonstrate. Since the activ ation of naive T cells has been shown to be initiated primarily by dendriti c cells (DC), these cells represent a potential target for TCDD immunotoxic ity. In this report, we have examined the influence of TCDD exposure on spl enic DC phenotype and function in the absence of antigenic stimulation. Res ults showed that DC from TCDD-treated mice expressed higher levels of sever al accessory molecules including ICAM-1, CD24, B7-2, and CD40, whereas the expression of LFA-1 was significantly reduced. These effects were dose-depe ndent and persisted for at least 14 days after exposure. The effects were a lso dependent upon the aryl hydrocarbon receptor (AhR), as similar effects were observed in AhR(+/+) C57Bl/6 and Balb/c mice but not in AhR(-/-) mice. When DC from TCDD-treated mice were cultured with allogeneic T cells, the proliferative response and production of IL-2 and IFN-gamma by the T cells were increased. Production of IL-12 by the DC was likewise enhanced in comp arison to cells from vehicle-treated mice. Interestingly, however, the numb er of DC recovered from TCDD-treated mice was significantly decreased. Take n together, these results suggest that, in the absence of antigen, TCDD pro vides an activation stimulus to DC that may lead to their premature deletio n. Since the survival of DC has been shown to influence the strength and du ration of the immune response, these results suggest a possible novel mecha nism for TCDD-induced immune suppression. (C) 2001 Academic Press.