TCDD exposure differentially alters antigen-specific IgA levels when given before or after immunization

Abstract

Abstract In mice, activation of the aryl hydrocarbon receptor (AhR) prior to primary antigen challenge can suppress antigen-specific serum IgM and IgG responses. Secondary antibody responses have been reported to be refractory to AhR-mediated suppression. Using ELISAs and female C57Bl/6 mice pretreated with the prototypic AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 40 μg/Kg in peanut oil) one day prior to oral cholera toxin (CT) immunization (10 μg, repeated weekly), we demonstrated significant suppression of CT-specific IgA levels in the feces after two weeks (by 64.4%); however, fecal IgA levels recovered to control levels by week four. Unlike fecal IgA levels, CT-specific serum IgA levels remained significantly suppressed (by 37.1%) through week four. At that time-point, when compared to control mice, the spleens of TCDD-treated mice contained 40.4% fewer leukocytes, and contained 66.4% fewer IgA+ plasma cells (analyzed by ELISpot) (all significantly different). When TCDD exposure was delayed for three weeks after beginning CT immunization, in comparison to control mice, serum CT-specific IgA levels were significantly suppressed by 33.2%, but fecal CT-specific IgA levels were not different, as in TCDD pre-treated mice. Because enhanced migration of some T cells into the gut has been reported after AhR activation, one explanation for the differential effect of TCDD exposure on CT-specific IgA levels when given either before and after immunization could be enhanced migration of plasma cells away from reticuloendothelial tissues and into mucosal tissues.