Mercury-induced renal autoimmunity in BN-->LEW.1N chimeric rats.
Repeated exposure to relatively low doses of mercuric chloride causes a variety of autoimmune responses in rats of the Brown Norway (BN) strain. These animals experience a membranous glomerulonephritis, characterized by the production of autoantibodies to renal antigens (e.g., laminin) and proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury. Despite extensive investigations, the mechanisms of immunoregulation in this animal model are still unknown. RT6+ T lymphocytes may have a regulatory role in both BN and LEW rats. This hypothesis is suggested by our finding of a mercury-associated decrease of RT6+ T cells in lymph nodes of BN rats exposed to mercury and the lack of such effect in similarly treated LEW rats. In the present report we show that congenic LEW.1N or BN.1L had no renal autoimmune disease after treatment with HgCl2. FCM analysis of mercury-treated LEW.1N revealed that RT6.1+ T lymphocytes were significantly decreased in both spleen and lymph nodes of these animals. Experimental depletion of RT6+ T cells (by monoclonal antibody treatment or gamma irradiation) in LEW.1N and BN.1L rats did not favor the induction of renal autoimmunity after exposure to mercury. On the other hand, BN-->LEW.1N chimeras (obtained by adoptive transfer of BN lymphocytes into gamma-irradiated LEW.1N rats) experienced autoimmune responses to kidney antigens when treated with HgCl2. They had autoantibodies to laminin and linear binding of immunoglobulins in their kidneys as well as a decreased percentage of RT6.2+ T lymphocytes in cervical lymph nodes. Therefore, the different components of this experimental model can now be dissected using various types of BN-->LEW.1N chimeras, obtained by the adoptive transfer of purified T cell subsets.
Kosuda
L L
LL
Department of Pathology, University of Connecticut Health Center, Farmington 06030.
Greiner
D L
DL
Bigazzi
P E
PE
D036002:ADP Ribose Transferases; D000818:Animals; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D002678:Chimera / Q000276:immunology*; D005260:Female; D005720:Gamma Rays; D006649:Histocompatibility Antigens; D016219:Immunotherapy, Adoptive; D007668:Kidney / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000528:radiation effects; D008562:Membrane Glycoproteins; D008627:Mercuric Chloride / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D008627:Mercuric Chloride; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat