Reduced T-helper cell function in mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Antibody production to the T-dependent antigen SRBC is highly sensitive to suppression by polychlorinated dibenzo-p-dioxins. The present study provides evidence for a defect in T-helper (TH) cells in TCDD-exposed mice. Because spleen cells from nonimmune TCDD-exposed mice did not show suppressed antibody responses when adoptively transferred to irradiated hosts, we used a hapten-carrier (TNP-SRBC) system with cell separation/reconstitution techniques to determine the effects of TCDD on carrier-specific TH cells. In vitro cultures of spleen cells from SRBC-primed TCDD-treated (5 micrograms/kg) mice produced fewer anti-TNP plaque-forming cells (PFC) when immunized with TNP-SRBC, as compared to cells from primed vehicle-treated controls. A reduced anti-TNP PFC response was also observed in experiments where non-immune B-cells were induced to produce anti-TNP PFC by TH-cells obtained from carrier-primed TCDD-exposed mice, as compared to carrier-primed vehicle-exposed mice. Removal of Lyt-2+ (suppressor) T-cells in these experiments did not alter the anti-TNP PFC response. These results provide direct evidence for reduced activity of TH-cells after exposure to TCDD.