Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: II. Effects on the pup and the adult.

Our recent work showed that in utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure produced alterations in fetal and neonatal thymocyte subpopulations. This study was designed to determine the persistence and functional significance of these alterations. One group of timed-bred pregnant F344 rats was dosed with 3.0 mcg TCDD/kg by gavage on gestational day 14 (GD14). The immune function of the perinatally-exposed offspring and age-matched controls were assessed at 14-17 weeks old. Examination of the organ weights and splenic phenotypes showed that TCDD exposure increased the spleen/body weight ratio, decreased the thymus/body weight ratio, and decreased the percentage of splenic CD3+/CD4-CD8- cells in both genders. The delayed-type hypersensitivity (DTH) response to bovine serum albumin (BSA) was suppressed in both the TCDD-exposed males and females. The lymphoproliferative (LP) responses to T-cell and B-cell mitogens and the antibody response to sheep red blood cells were not affected by perinatal TCDD exposure in either gender except for a suppressed LP response to PWM in the females. A second set of timed-pregnant F344 rats was dosed with 0 or 1.0 mcg TCDD/kg on GD14. One day after birth litters were cross-fostered to produce control, placental-only, lactational-only, and placental/lactational exposure groups. The organ weights and thymic and splenic phenotypes of these pups were assayed 1, 2, or 3 weeks post-partum, while the DTH response was assessed in 5-month-old males. Increased liver/body weight ratios, decreased percentages of thymic CD3+/CD4-CD8- cells, and increased percentages of thymic CD3+/CD4-CD8+ cells were seen through 3 weeks old in both genders after TCDD exposure. The severity of the effects was related to the route of exposure (i.e. placental/lactational > lactational > placental). The DTH response to BSA was suppressed in the males receiving both placental and lactational exposure. These results suggest that the immunotoxic effects of perinatal TCDD exposure of rats persist into adulthood and that suppression of the DTH response may represent the most sensitive biomarker for TCDD-induced immunotoxicity in this species.