IMMUNOSUPPRESSIVE EFFECTS OF HIGHLY CHLORINATED BIPHENYLS AND DIPHENYL ETHERS ON T-CELL-DEPENDENT AND INDEPENDENT ANTIGENS IN MICE

The dose-dependent effects of 2,2',3,3 ',4,4',5,5',6-nonachlorobipheny l (nonaCB), 2,2',3,3',4,4',5,6,6'-nonaCB, 2,2',3,3',4,5,5',6,6'-nonaCB and decaCB on the suppression of the splenic plaque-forming cell (PFC ) response to the T-cell-dependent antigen, sheep red blood cells (SRB Cs) and the T-cell-independent antigen, trinitrophenyl-lipopolysacchar ide (TNP-LPS), were determined in genetically inbred mice. In addition , the induction of hepatic microsomal ethoxyresorufin O-deethylase (ER OD) activity was also measured. The highly chlorinated biphenyls suppr essed the splenic PFC response to SRBCs in C57BL/6 and DBA/2 mice and were relatively more active in the former strain. The C57BL/6 mice are more responsive to aryl hydrocarbon (Ah) receptor agonists than DBA/2 mice and these data support a possible role for the Ah receptor in me diating this response. However, previous studies with polychlorinated biphenyls (PCBs) indicate that congeners with 3 or 4 ortho-chloro subs tituents are inactive as Ah receptor agonists and this was consistent with the minimal induction of hepatic microsomal EROD activity by the highly chlorinated biphenyls in both strains of mice. Thus, the result s suggest that the inhibition of the splenic PFC response to SRBCs obs erved in this study was primarily an Ah receptor-independent response. Some of the highly chlorinated diphyenyl ethers namely decachlorodiph enyl ether and 2,2',3,3 ',4,4',5,6,6'-nonachlorodiphenyl ether, inhibi ted the antigenic response to TNP-LPS in C57 BL/6 mice. The results in dicate that the suppression of the TNP-LPS-mediated immune response ma y be a more reliable indicator of the Ah receptor-dependent immunotoxi city of halogenated hydrocarbons.