Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity and lymphocyte subpopulations: differences between mice and rats.
While the effect that TCDD has on humoral immunity has been well documented for the mouse, it has not been for the rat. In this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. The effect that TCDD has on the PFC response of male F344 and female Long-Evans rats was also determined. Mice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 micrograms/kg, 7 days prior to intravenous immunization with SRBC. Four days later the PFC response to SRBC was determined. Mice showed a dose-related suppression of the PFC response, with an ED50 of 0.7 micrograms/kg TCDD. In contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 micrograms/kg. The inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 microgram/kg TCDD, respectively. There was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. Phenotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10, or 30 micrograms/kg) and SRBC-immunized mice and rats revealed that CD4-CD8+ splenocytes were reduced in a dose-related manner in rats only and that this reduction in CD4-CD8+ was accompanied by a dose-related increase in IgM+ splenocytes. These results demonstrate species differences in the effect of TCDD on the PFC response to SRBC which were unrelated to hepatic CYP1A1 or CYP1A2 induction, time to peak response, gender, and strain. The failure of TCDD to suppress and in fact to enhance the PFC response to SRBC in rats appears to be related to alterations in splenic CD4-CD8+ lymphocytes.
Smialowicz
R J
RJ
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Riddle
M M
MM
Williams
W C
WC
Diliberto
J J
JJ
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System