Enhanced Suppressor Cell Activity as a Mechanism of Immunosuppression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

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Abstract
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic halogenated aromatic hydrocarbon, acts in the body as a cumulative poison. The chronic immunotoxic effects of TCDD were studied in C57B1/6 male mice. Total doses of 100 μg/kg or greater produced cellular depletion in thymus, spleen, and lymph nodes, and the animals appeared sick. No cellular depletion was seen following 0.4 μg/kg, and only thymus was affected by 4 and 40 μg/kg. The antibody response to SRBC and TNP-Brucella abortus was impaired following 40μg/kg TCDD, the delayed hypersensitivity response to oxazalone was impaired by 4 μg/kg and the generation of alloantigen-specific cytotoxic T cells (CTL) was sensitive to as little as 0.004 μg/kg TCDD. In vitro analysis of the mechanism of suppression using limiting dilution techniques showed that TCDD did not deplete the precursors of CTL but generated cells capable of suppressing CTL generation in vitro.