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Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors
Published on: March 17, 2014
2,3,7,8-Tetrachlorodibenzo-p-dioxin affects the number and function of murine splenic dendritic cells and their
B A Vorderstrasse1, N I Kerkvliet
1Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, USA.
Abstract:
Primary T cell-mediated immune responses are highly susceptible to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, yet direct effects of TCDD on T cells have been difficult to demonstrate. Since the activation of naive T cells has been shown to be initiated primarily by dendritic cells (DC), these cells represent a potential target for TCDD immunotoxicity. In this report, we have examined the influence of TCDD exposure on splenic DC phenotype and function in the absence of antigenic stimulation. Results showed that DC from TCDD-treated mice expressed higher levels of several accessory molecules including ICAM-1, CD24, B7-2, and CD40, whereas the expression of LFA-1 was significantly reduced. These effects were dose-dependent and persisted for at least 14 days after exposure. The effects were also 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 comparison to cells from vehicle-treated mice. Interestingly, however, the number of DC recovered from TCDD-treated mice was significantly decreased. Taken together, these results suggest that, in the absence of antigen, TCDD provides an activation stimulus to DC that may lead to their premature deletion. Since the survival of DC has been shown to influence the strength and duration of the immune response, these results suggest a possible novel mechanism for TCDD-induced immune suppression.
Insights
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters dendritic cell (DC) function and phenotype, potentially leading to immune suppression. TCDD activates DCs, increasing T cell responses but reducing DC numbers, suggesting premature deletion.
Area of Science:
- Immunology
- Environmental Toxicology
- Cell Biology
Background:
- Primary T cell responses are vulnerable to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppression.
- Dendritic cells (DCs) initiate naive T cell activation, making them a potential target for TCDD immunotoxicity.
Purpose of the Study:
- To investigate the impact of TCDD exposure on splenic DC phenotype and function without antigenic stimulation.
- To elucidate the role of the aryl hydrocarbon receptor (AhR) in TCDD's effects on DCs.
Main Methods:
- Mice were exposed to varying doses of TCDD.
- Splenic DCs were analyzed for phenotype (accessory molecule expression) and function.
- DC-T cell co-cultures were performed to assess T cell proliferation and cytokine production.
- AhR-deficient mice were used to determine receptor dependency.
Main Results:
- TCDD exposure increased DC expression of ICAM-1, CD24, B7-2, and CD40, while decreasing LFA-1, in an AhR-dependent manner.
- TCDD-treated DC enhanced allogeneic T cell proliferation and IL-2/IFN-gamma production.
- IL-12 production by DCs was also enhanced following TCDD exposure.
- A significant decrease in the number of DCs was observed in TCDD-treated mice.
Conclusions:
- TCDD acts as an activation stimulus for DCs in the absence of antigen, mediated by the AhR.
- This TCDD-induced DC activation may lead to premature DC deletion, impacting immune response strength and duration.
- These findings suggest a novel mechanism for TCDD-mediated immune suppression via DC modulation.
