Sensitivity to suppression of cytotoxic T cell generation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on the Ah genotype of the murine host.
Susceptibility of mice to a variety of toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is genetically determined by the Ah locus. To determine if immunotoxicity following TCDD exposure was also regulated by the Ah locus, we tested the ability of low dose TCDD (4 ng/kg) to suppress the generation of allospecific cytotoxic T cells (CTL) by lymphocytes from "susceptible" C57B1/6, and "resistant" DBA/2, and from C57B1/6XDBA/2J F1 hybrid mice in vitro. To determine if TCDD acted directly on the "susceptible" lymphoid cells, the immune response of C57B1/6 leads to DBA/2 and DBA leads to C57B1/6 bone marrow chimeras was also measured. C57B1/6 and F1 mice proved susceptible to suppression consistent with the dominant effect of Ah. Susceptibility to suppression in chimeric mice, however, was determined by the Ah genotype of the host and not by the genotype of the grafted lymphomyeloid cells. Mixing experiments demonstrated that suppression of CTL generation by TCDD was due to suppressor T cells. The frequency of CTL precursors was not affected by TCDD. These results are consistent with the idea that TCDD acts by an Ah locus-dependent mechanism to indirectly promote development of suppressor T cells that block the generation of CTL from their precursors.
D000818:Animals; D004147:Dioxins / Q000633:toxicity*; D005838:Genotype; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D004147:Dioxins; D007166:Immunosuppressive Agents; D000072317:Polychlorinated Dibenzodioxins