Increased class I and class II MHC products and mRNA in kidneys of MRL-lpr/lpr mice during autoimmune nephritis and inhibition by cyclosporine.
The expression of MHC products in the kidneys of MRL-1pr/1pr mice was investigated. As previously described, these mice develop lupus-like nephritis with intraglomerular and peritubular Ig deposition, vasculitis, and interstitial mononuclear cell infiltration at about 12 wk of age. As the nephritis appeared, the expression of MHC class I and II products rose, as demonstrated by absorption and by specific binding of radiolabeled antibodies. Hybridization of kidney RNA with specific probes revealed an increase in specific mRNA for MHC class I and II genes and for beta2 microglobulin. Using rat monoclonals against mouse class I and II MHC products, and goat anti-rat Ig as second antibody, we showed that the increase in renal class I and II expression was localized to the basolateral membranes of tubular cells, and, in the case of class I, in arteries and glomeruli. The sites of tubular MHC expression corresponded closely to the sites of extensive peritubular Ig deposition. High doses of cyclosporine given for 6 to 8 wk reduced the peritubular Ig deposits, renal Ia and H-2K expression, and specific mRNA for beta 2-microglobulin and MHC genes, but did not reduce anti-DNA antibody levels in serum. Thus the peritubular Ig deposits and tubular MHC induction coincided in timing and location, and in their resolution with cyclosporine. The results raise the possibility that the increase in renal MHC expression not only accompanies the renal lesions, but may play a role in their pathogenesis.
D000818:Animals; D000911:Antibodies, Monoclonal; D001666:Binding Sites, Antibody; D002465:Cell Movement; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000276:immunology; D007136:Immunoglobulins / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D012333:RNA, Messenger; D001613:beta 2-Microglobulin