The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10 transgenic CD4(+) T cells in adoptively transferred mice

Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-diox in (TCDD) suppresses the generation of T cell-dependent immunity, both humo ral and cell-mediated. However, the mechanism of TCDD-induced immune suppre ssion remains to be defined. We hypothesized that exposure to TCDD suppress es the activation of naive CD4(+) T cells and prevents their expansion and differentiation into effector T-helper cells capable of driving T cell-depe ndent immune responses. To test this hypothesis, we adoptively-transferred DO11.10 OVA-specific T-cell receptor (TCR) transgenic T cells into syngenei c recipients and used a TCR-specific monoclonal antibody to track the in vi vo activation of naive CD4(+) T lymphocytes following exposure to OVA. The production of OVA-specific antibodies was suppressed in a dose-dependent ma nner in adoptively transferred mice that had been exposed to TCDD. Although TCDD exposure had little effect on the expansion or activation of the adop tively transferred, OVA-specific CD4(+) T cells, these cells disappeared fr om the spleen more rapidly in TCDD-treated mice and produced significantly decreased levels of the T cell-derived cytokines IL-2 and IL-10. There was also a trend towards reduced IFN-gamma and IL-4 production following in vit ro re-stimulation. These data suggest that TCDD may interfere with the surv ival and/or differentiation of OVA-specific T-helper cells. These results d emonstrate for the first time the potential of the DO11.10 adoptive transfe r system to directly assess immunotoxic effects of xenobiotics on antigen-s pecific CD4(+) T cells in vivo.