Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin

Abstract

Recently we observed a suppressed delayed-type hypersensitivity (DTH) response to bovine serum albumin (BSA) in the 4–5-month-old offspring of F344 rat dams receiving as little as 1.0 μg 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)/kg on gestational day (GD) 14. This study was designed to characterize better this suppression of the DTH response. First, the persistence of the DTH suppression was determined by measuring the DTH response to BSA in the offspring of dams dosed orally with 3.0 μg TCDD/kg on GD14 as well as in age-matched controls at 4, 8, 12 and 19 months of age. TCDD significantly suppressed the males’ DTH response through 19 months of age. While the females’ DTH response was reduced at 8, 12 and 19 months, significant suppression was observed only at 4 months of age. Secondly, the lowest maternal dose of TCDD that produced DTH suppression was determined by measuring the DTH response to BSA in the 4- and 14-month-old offspring of dams dosed orally with 0, 0.1, 0.3 or 1.0 μg TCDD/kg on GD14. In the males, suppression was observed at a maternal dose as low as 0.1 μg TCDD/kg at 14 months of age, while a maternal dose of 0.3 μg TCDD/kg was necessary to cause suppression in the 14-month-old females. Both males and females were more sensitive to the suppression at 14 months of age than at 4 months of age. Lastly, the DTH response to a second antigen was examined by measuring the DTH response to either BSA or keyhole limpet hemocyanin (KLH) in the 5- or 4-month-old male offspring, respectively, of dams dosed orally with either 0 or 3.0 μg TCDD/kg on GD14. The DTH response to both antigens was suppressed significantly. Phenotypic analysis was performed on thymus and lymph node suspensions. Significant effects in the thymus included an increased percentage of γδ TCR + cells and a decreased percentage of γδ TCR +/CD4 −CD8 − and MHCI − MHCII − cells. In the popliteal lymph node draining the BSA-injected footpad, there was a decreased percentage of γδ TCR + and MHCI −MHCII − cells and an increased percentage of MHCI + cells. In conclusion, the suppression of the DTH response associated with perinatal TCDD exposure is persistent through late adulthood, occurs at a low dose (i.e. 0.1 μg TCDD/kg) to the dam, and is more pronounced in males than females. While phenotypic analysis identified differences in subsets of thymocytes and lymph node cells between control and TCDD exposed offspring, no clear correlations were established between altered subpopulations and suppressed DTH responses.