SUPPRESSION OF HUMORAL ANTIBODY-PRODUCTION BY EXPOSURE TO 1,2,3,6,7,8-HEXACHLORODIBENZO-PARA-DIOXIN

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (3) , 518-526
Abstract
The day 4 IgM antibody (AB) response to sheep red blood cells was suppressed in adult female B6C3F1 mice subchronically (14 day) exposed to 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,2,3,6,7,8-HCDD) at concentrations reflecting the levels of this dioxin isomer as a contaminant in technical-grade pentachlorophenol. Hepatic microsomal parameters were also measured in these mice and indicated that characteristic induction of mixed-function oxidase enzyme activities, particulary aryl hydrocarbon hydroxylase. The response to sheep red blood cells was also suppressed when measured in vitro by culturing the antigen with spleen cells from a second group of mice subchronically exposed to 1,2,3,6,7,8-HCDD. Enumeration studies with fluorescent-labeled antisera in these animals indicated a dose-related suppression in the number of T-lymphocytes with no effect on B-lymphocytes. 1,2,3,6,7,8-HCDD directly suppressed several in vitro AB responses when added to cultures of spleen cell suspensions from untreated B6C3F1 mice. The rank order of sensitivity was determined to be: polyclonal AB response to LPS [lipopolysaccharide] .gtoreq. T-independent AB response to DNP[dinitrophenyl]-Ficoll > T-dependent AB response to sheep red blood cells. Subsequent studies indicated that the suppression by 1,2,3,6,7,8-HCDD could be produced after only a 30-min preincubation. The suppression of all in vitro AB responses was abolished when the dioxin was preincubated with a metabolic activation system, i.e., crude liver homogenate (B6C3F1 mice pretreated with the mixed-function oxidase inducer, Aroclor 1254) plus NADP and isocitrate. The suppression of the T-dependent AB response was still evident when the metabolic activation system was heat-inactivated (as verified by an inability to activate cyclophosphamide) prior to the preincubation.

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