Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 1. Effects on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus) after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Monoclonal antibodies were used to analyse the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral lymphocytes from marmosets (Callithrix jacchus) following injections of single low doses of TCDD. A reduction of the percentage and the total number of lymphocytes among the white blood cells was seen 3 weeks after a single administration of 300 ng TCDD/kg body wt, but not following 167 ng TCDD/kg or less. After treatment of marmosets with the single subcutaneous dose of 10 ng TCDD/kg body wt. we observed an average decrease of about 20% in the percentage of CD4+ cells in the venous blood of treated animals. This change was not seen at the time of maximum absorption (2 weeks after the injection), but was demonstrable after 4 weeks and reached its maximum 15 weeks after the injection. The time course of the changes suggests an indirect effect (possibly via the thymus). Due to the considerable inter- and intra-individual variability in the number of peripheral lymphocytes the effect was less convincing on the basis of the total CD4+ cells per microliter blood. There was a significant concomitant increase in the percentage of cells with the CD8+ marker. A closer analysis of the lymphocyte subpopulation involved revealed a predominant effect on the cells with the CD4CDw29 ("leu 3a+4B4+") surface marker ("helper-inducer cells"). Subsequent to a dose of 10 ng TCDD/kg body wt the percentage of these cells was reduced by 50% or more when compared with the (24) controls. On an absolute basis (number of cell/microliter blood) these CD4+CDw29+ cells were clearly reduced in only two out of four marmosets. There was no significant effect on the percentage of the CD4+CD45R+ ("leu3a+2H4+") subpopulation ("suppressor-inducer cells"). The ratios: CD4+CDw29+/CD4+CD45R+, or CD4+CDw29+/CD8+ appear to be convenient measures for monitoring the effect described. Since the difference between the percentage of CD2+ cells minus the sum of CD4+ plus CD8+ cells was found to be increased following rather high doses (167 ng TCDD/kg body wt or more), this suggests that immature cells (CD2+ CD4-CD8-) are released into the periphery as a result of the exposure to TCDD. Furthermore, a decrease in the percentage of CD20+ (B1+) cells (about 50% when compared with controls) was observed in the treated animals following a single dose of 10 ng TCDD/kg body wt or higher. Subsequent to a dose of 10 ng TCDD/kg body wt the percentage of CD56+ (NKH1+) cells seemed to be slightly increased. The dose-response for the effects observed was rather poor.(ABSTRACT TRUNCATED AT 400 WORDS)
Neubert
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Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin.
Jacob-Müller
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Stahlmann
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Helge
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Neubert
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D000818:Animals; D000954:Antigens, Surface; D001402:B-Lymphocytes / Q000187:drug effects; D001572:Benzofurans / Q000633:toxicity*; D002144:Callithrix; D004147:Dioxins / Q000633:toxicity*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects
D000954:Antigens, Surface; D001572:Benzofurans; D004147:Dioxins; D008934:Mitogens; D000072317:Polychlorinated Dibenzodioxins