title: Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity.
abstract: Chemically induced autoimmunity is a recently recognized environmental hazard that may affect individuals genetically predisposed to autoimmune disease and chronically exposed to certain chemicals. For example, moderate concentrations of mercury may lead to renal autoimmune disease in a small but significant percentage of the exposed population. Mercury also induces autoimmune glomerulonephritis in susceptible Brown Norway (BN) and MAXX inbred strain rats. Autoimmune responses, directed to epitopes of the renal glomerular basement membrane (GBM), are rapid in onset and have a self-limiting course in mercury-treated rats. Both regulatory T cells and idiotype-anti-idiotype network have been implicated in the resolution of this autoimmune process. In our investigations of immune regulation of mercury-induced autoimmune glomerulonephritis, we have used flow cytometry to quantitate lymphocyte subpopulations in the spleen and lymph nodes of mercury-treated and control BN rats. Of particular interest was the RT6+ T cell subset, that appears to have important immunoregulatory properties in a rat model of autoimmune insulin-dependent diabetes mellitus. Spleen and lymph nodes from control BN rats contained 22 and 52%, respectively, RT6+ cells. Spleens from mercury-treated animals contained 21% RT6+ cells on Day 10 of treatment, 13% on Day 17, 16% on Day 24 and 20% on Day 30. Lymph nodes from the same rats had 36% RT6+ cells on Day 10, 23% on Day 17, 29% on Day 24, and 28% on Day 30. The decrease in RT6+ cells correlated inversely with autoimmune responses to GBM, which peaked on Days 17-24 and declined by Day 30. Moreover, autoimmune responses were also associated with elevated RT6-:RT6+ T cell ratios. Similar results were obtained in two additional groups of BN rats, comprising both younger and older animals, sacrificed at Day 18 of mercury treatment. Analysis of other lymphocyte subpopulations demonstrated a decrease of CD4+ and CD5+ cells, whereas B cells as well as CD8+, IL-2 receptor+, and MHC class II+ subsets showed no consistent correlation with the onset or resolution of the autoimmune process. These findings suggest that mercury-induced changes in RT6+ T lymphocytes may be related to the development of renal autoimmune disease in genetically predisposed BN rats.
authors.affiliation: Department of Pathology, University of Connecticut Health Center, Farmington 06030.
authors.forename: L L
authors.initials: LL
authors.lastname: Kosuda
authors.forename: A
authors.initials: A
authors.lastname: Wayne
authors.forename: M
authors.initials: M
authors.lastname: Nahounou
authors.forename: D L
authors.initials: DL
authors.lastname: Greiner
authors.forename: P E
authors.initials: PE
authors.lastname: Bigazzi
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D015551:Autoimmunity / Q000187:drug effects*; D001485:Basement Membrane / Q000276:immunology; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008562:Membrane Glycoproteins; D008628:Mercury / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat; D008628:Mercury