Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In experimentally exposed animals 2,3,7,8-tetrachlorodibenzo-n-dioxin (TCDD) causes severe immunosuppression. However, the overall susceptibility of humans for the different pathological effects of TCDD has remained unclear. We examined the long-term effects of TCDD in 11 industrial workers who were exposed to high doses of TCDD for several years 20 years ago. Current TCDD body burdens were still at least 10 times higher (between 43 and 874 pg/g blood far) in these exposed persons than in the average German population. To evaluate possible TCDD-induced changes in the percentage of different lymphocyte subsets, we determined a large panel of lymphocyte subsets in the blood by flow cytometric analysis. Immunocompetence of T-and B-lymphocytes was tested by nitrogen (phytohemagglutinin, pokeweed mitogen)- induced lymphoproliferation assays and by assays using sensitive mixed-lymphocyte cultures. No significant differences could be detected between the individuals tested and controls for surface marker distribution or mitogen-induced lymphoproliferation TCDD-exposed subjects showed a reduced response to human lymphocyte antigen-allogeneic lymphocytes and interleukin-2-boosted proliferation. Responder cells of the dioxin-exposed persons proliferated less in response to irradiated stimulator cells (p < or = 0.05), and the third-party mixed lymphocyte reaction against unirradiated stimulator cells revealed suppressive activity in the responder cell fraction compared to the controls (p < or = 0.01). Furthermore, the capacity of a pool of T cells isolated from TCDD-exposed subjects to proliferate upon interleukin-2 stimulation was significantly diminished (p < or = 0.05). TCDD has a long-term immunosuppressive-effect on T-helper cell function, which is mediated more likely by a reduced functionality of individual cells rather than by a reduction in absolute cell numbers in the peripheral blood.