Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus).
The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on poke weed mitogen-stimulated proliferation and differentiation of peripheral lymphocytes was studied in vitro with cells from a non-human primate (marmoset monkey, Callithrix jacchus) and from man. Monoclonal antibodies and flow cytometry (FACScan) were used for analysis. The extent of the overall mitogen-stimulated proliferation of isolated lymphocytes in vitro from marmoset blood was only slightly reduced in the presence of TCDD compared to the solvent control (0.01% DMSO). However, incubation with TCDD in the culture medium together with the mitogen led to a pronounced decrease in the percentage of the lymphocyte subset with the surface marker CD4, and a concomitant increase in the percentage of CD8+ cells. The lowest concentration found to be effective in vitro was 1 x 10(-13) M TCDD (25 fg TCDD/ml). When culturing lymphocytes from human blood of different donors under identical conditions in the presence of TCDD and the mitogen, corresponding effects were observed to those seen with marmoset cells. A closer analysis of the T lymphocyte subsets affected revealed the CD4+ CDw29+ (helper-inducer cells) to be the main target for the action of TCDD. A clear-cut change in the percentage of this subpopulation was induced at concentrations as low as 1 x 10(-13) M TCDD. The development of the IL-2-marker in culture was only slightly affected by TCDD, and concentrations of 1 x 10(-12) M were required to slightly reduce the number of CD2+CD25+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Neubert
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R
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Jacob-Müller
U
U
Helge
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H
Stahlmann
R
R
Neubert
D
D
D000818:Animals; D002143:Callitrichinae; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
D000072317:Polychlorinated Dibenzodioxins