PERSISTENCE OF DECREASED T-HELPER CELL-FUNCTION IN INDUSTRIAL-WORKERS20 YEARS AFTER EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

In experimentally exposed animals, 2,3,7,8,-tenachlorodibenzo-p-dioxin (TCDD) causes severe immunosuppression. However, the overall suscepti bility of humans for the different pathological-effects of TCDD has re mained unclear. We examined the long-term effects of TCDD in 11 indust rial 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 h igher (between 43 and 874 pg/g blood fat) in these exposed persons tha n in the average German population, To evaluate possible TCDD-induced changes in the percentage of different lymphocyte subsets, we determin ed a large panel of lymphocyte subsets in the blood by flow cytometric analysis. Immunocompetence of T- and B-lymphocytes was tested by mito gen (phytohemagglutinin, pokeweed mitogen)-induced lymphoproliferation assays and by assays using sensitive mixed-lymphocyte cultures. No si gnificant differences could be detected between the individuals tested and controls for surface marker distribution or mitogen-induced lymph oproliferation. TCDD-exposed subjects showed a reduced response to hum an lymphocyte antigen-allogeneic lymphocytes and interleukin-2-boosted proliferation. Responder cells of the dioxin-exposed persons prolifer ated less in response to irradiated stimulator cells (p less than or e qual to 0.05), and the ''third-party'' mixed lymphocyte reaction again st unirradiated stimulator cells revealed suppressive activity in the responder cell fraction compared to the control (p less than or equal to 0.01). Furthermore, the capacity of a pool of T-cells isolated from TCDD-exposed subjects to proliferate upon interleukin-2 stimulation w as significantly diminished (p less than or equal to 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 r ather than by a reduction in absolute cell numbers in the peripheral b lood.