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

Abstract

Antibody production to the T-dependent antigen SRBC is highly sensitive to suppression by polychlo-rinated dibenzo- p-dioxins. The present study provides evidence for a defect in T-helper (T H) 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 T H cells. In vitro cultures of spleen cells from SRBC-primed TCDD-treated (5 μg/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 T H-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 T H-cells after exposure to TCDD.