Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype.
Mercuric chloride (HgCl2) induces in Brown Norway rats a CD4+ T lymphocyte-dependent systemic autoimmune syndrome, involving synthesis of anti-glomerular basement membrane autoantibodies and development of proteinuria. Lewis rats are resistant to HgCl2-induced autoantibody production and, in contrast, develop immunosuppression, mediated by CD8+ T lymphocytes. In the present study, genetic requirements governing autoreactivity or immunosuppression in response to HgCl2 were further explored. Both major histocompatibility complex (MHC) and non-MHC genes are involved in determining susceptibility to HgCl2-induced autoimmunity. Both AO (RT1u) and DZB (RT1u) rats were found to develop a membranous autoimmune glomerulopathy upon exposure to HgCl2. Only the DZB strain, which differs in part of the non-MHC background from AO, developed proteinuria. AO.1P (RT1.AuB1D1Eu) rats, which are genetically identical to AO except for the Lewis haplotype at the MHC class II loci, appeared to develop immunosuppression upon exposure to HgCl2. It is concluded that autoreactivity and immunosuppression, induced by HgCl2, are both dependent on the MHC class II haplotype. In autoimmune responder strains the type of autoimmune glomerulopathy is influenced by non-MHC genes.
Aten
J
J
Department of Pathology, University of Leiden.
Veninga
A
A
De Heer
E
E
Rozing
J
J
Nieuwenhuis
P
P
Hoedemaeker
P J
PJ
Weening
J J
JJ
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007108:Immune Tolerance / Q000187:drug effects*; D008285:Major Histocompatibility Complex; D008627:Mercuric Chloride / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000949:Histocompatibility Antigens Class II; D008627:Mercuric Chloride