Influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antigen-presenting activity of dendritic cells.
We have previously shown that exposure of mice to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) induces activation-like changes in splenic dendritic cells (DC) in the absence of antigen challenge. Since activation of DC reduces their ability to phagocytize antigen, we examined the effects of TCDD on the ability of DC to process and present antigen to antigen-specific T cells and to internalize latex beads. Additionally, the expression of costimulatory and adhesion molecules was examined on DC from TCDD-treated mice injected with allogeneic tumor cells. The ability of DC from C57Bl/6 mice to induce proliferation of keyhole limpet hemocyanin (KLH)-specific 10.5.17 T cells and production of IL-4 was not significantly altered by TCDD exposure, either when KLH was added in vitro or when the mice were injected with KLH prior to DC isolation. In contrast, ovalbumin (OVA) presentation by DC from TCDD-treated Balb/c mice induced enhanced proliferation of OVA-specific D011.10 T cells, although the production of IL-2 and IFN-gamma was not affected. Enhanced in vivo proliferation of adoptively transferred, CFSE-labeled DO11.10 T cells was also observed in TCDD-treated Balb/c mice that were challenged with OVA. TCDD treatment modulated the expression of major histocompatibility complex (MHC) class II, CD24, ICAM-1, CD40, and LFA-1 on splenic DC from C57Bl/6 mice injected with allogeneic tumor cells; however, the effects of TCDD were identical to changes seen previously in nonimmune mice, suggesting that these effects were not antigen-dependent. Finally, TCDD treatment did not affect the ability of splenic DC to internalize latex beads administered in vivo. Taken together, these results suggest that the activation-like changes induced in DC by TCDD do not suppress the ability of DC to process and present antigen, but may enhance their ability to provide activation signals to T cells. This, in turn, may alter the survival of the T cells, the DC, or both, and might lead to dysregulation of the immune response.
Vorderstrasse
Beth A
BA
Department of Environmental and Molecular Toxicology and Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon 97331, USA.
Dearstyne
Erica A
EA
Kerkvliet
Nancy I
NI
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006433:Hemocyanins / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects; D014184:Transplantation, Homologous / Q000379:methods; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin