Distinct immunomodulation by autoimmunogenic xenobiotics in susceptible and resistant mice

HgCl2 and diphenylhydantoin (DPH) are prototype chemicals associated with diverse (auto)immune effects in genetically susceptible individuals. Both chemicals activate T cells, and the balance of Th1 versus Th2 activation may influence the clinical outcome of exposure. It is unknown which chemically created neoantigens are responsible for Th activation. We therefore investigated the effect of DPH and HgCl2 on specific responses to TNP-ovalbumin, in mouse strains with varying sensitivity for the adverse effects. HgCl2 was found to enhance Th2-driven antibody responses in susceptible B10.s, but protective type 1 responses in resistant B10.d2 mice, This was chemical-specific, as DPH enhanced type 2 responses in both strains. DBA/2 mice were relatively unresponsive to HgCl2, whereas DPH stimulated type 1 responses in these mice, Interestingly, prior exposure to HgCl2, but not DPH, facilitated IC deposition in B10.s mice only, Thus, we demonstrate that, depending on MHC-II and background genes, HgCl2 and DPH preferentially adjuvate type 1 or type 2 responses. In case of HgCl2, the type of response corresponds with susceptibility to antibody-mediated autoimmunity induced by this chemical. In addition, we demonstrate that, within one strain, different autoimmunogenic chemicals can enhance distinct responses to the Same antigen. (C) 1999 Academic Press.