CHARACTERIZATION OF THE ROLE PLAYED BY ANTIGEN CHALLENGE IN THE SUPPRESSION OF IN-VIVO HUMORAL IMMUNITY BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

The goal of these studies was to characterize the role played by antig en challenge in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced imm unosuppression. The effects of single exposure to TCDD (4.2, 14, and 4 2 mu g/kg) in B6C3F1 mice on the reverse plaque assay (RPA; no sensiti zation) and the sheep red blood cell (SRBC) antibody response were com pared. While the RPA was suppressed in a dose-dependent fashion with s ignificance at the two highest doses, a much more dramatic effect was noted with the primary anti-SRBC response: a suppression was noted at the lowest dose, which was comparable to that observed with the highes t dose in the RPA. Subsequent studies compared the RPA in B6C3F1 (Ah-h igh responder) and DBA/2 (Ah-low responder) mice after both single and repeated exposure to identical cumulative doses of TCDD (4.2, 14, and 42 mu g/kg). The repeated exposures consisted of 14 consecutive daily treatments of 0.3, 1.0, and 3.0 mu g/kg. The results indicated only a slight difference in the effects of TCDD in the two strains after sin gle exposure, and even less difference after repeated exposure. Moreov er, administering TCDD on different days relative to the SRBC challeng e indicated a suppression in both strains when given 1, 2, or 3 days b efore antigen challenge, on the day of antigen challenge, or 1 or 2 da ys after antigen challenge. The only day of administration where the s uppression was attenuated was 3 days after antigen challenge. These re sults confirm an important relationship between antigen challenge and TCDD exposure on immunosuppression.