Cellular and genetic basis for suppression of cytotoxic T cell generation by haloaromatic hydrocarbons

TitleCellular and genetic basis for suppression of cytotoxic T cell generation by haloaromatic hydrocarbons
Publication TypeJournal Article
Year of Publication1983
AuthorsClark, DA, Sweeney, G, Safe, S, Hancock, E, Kilburn, DG, Gauldie, J
Pagination143 - 153
Date Published1983/08/01
ISBN Number0162-3109
KeywordsCytotoxic T lymphocytes, Environmental toxins, Haloaromatic hydrocarbons, Herpes virus infection, Suppressor cells, TCDD

Generation of allospecific cytotoxic T cells in C57Bl/6 mice is significantly impaired following exposure to TCDD at doses as low as 4 ng/kg. T helper activity, as assessed by the ability to produce Interleukin 2, and frequency of CTL precursors appear unaffected in treated animals and thus the TCCD-induced suppressor cells we have described are primarily responsible for the reduction in the CTL response. Suppression of CTL generation in DBA/2 mice requires a 10–100-fold greater dose than in C57B1/6, consistent with the observation that the Ah locus gene(s) of DBA/2 mice code for TCDD receptors with low binding affinity for TCDD. Other haloaromatic hydrocarbons (3,3′4,4′-tetrachlorobiphenyl and Aroclor 1254), capable of binding to the TCDD receptor, also suppress CTL generation, whereas the 2,2′,4,4′,6,6′-hexachlorobiphenyl molecule that lacks affinity for the TCDD receptor does not suppress CTL. The immunotoxic effects of TCDD in C57B/6 and DBA/2 mice occur at dose levels below those required to induce mixed-function oxidase enzymes in the liver. Suppression of CTL by TCDD is associated with increased susceptibility to lethal herpes virus type II infection. These data suggest that low levels of TCDD may interact with cytoplasmic receptors for TCDD in the thymus and induce biologically significant immunosuppression through activation of suppressor cells.

Short TitleImmunopharmacology