The time course of Heymann's
nephritis (HN), assessed on
proteinuria and immunomorphology, has been compared in Lewis (LEW) rats immunized with BB alone (group A) or injected with
HgCl2 and subsequently immunized in a similar manner (group B). Whereas all rats from group A developed typical HN characterized by heavy
proteinuria and abundant glomerular immune deposits, rats from group B did not develop or developed a markedly attenuated form of HN;
proteinuria was never detectable, immune deposits were absent or minimal. No abnormalities were found in rats injected with
HgCl2 alone. In order to explain our findings, we have studied the glomerular and tubular expression of the 330 kD
nephritogenic glycoprotein (gp330) as well as the corresponding antibody response. In rats receiving
HgCl2, gp330 was normally expressed on BB and glomerular epithelial cells as indicated by in vitro and in vivo binding of anti-gp330
antibodies, but titers of anti-BB and anti-gp330
antibodies were considerably lower than in group A control rats. These findings therefore suggest that
HgCl2 acts by its immunodepressive effect recently related to an increase in T suppressor cells. This effect is paradoxical since
HgCl2 induces autoimmunity in Brown-Norway rats, and we suggest that it may be akin to observations reported in clinical practice where drugs may be immunostimulatory in some patients and immunodepressive in others. The
mercury model may therefore represent a unique tool to evaluate the relationship between genetics and
drug-induced immune dysregulation.