The autoimmune response in active Heymann's nephritis in Lewis rats is regulated by T-lymphocyte subsets.
In this study the cellular events which are responsible for the induction and suppression of active Heymann's nephritis (HN) in Lewis rats were investigated. Using an enzyme-linked short-term culture assay specific autoantibody production in vitro by lymphoid cells directed against the nephritogenic renal tubular epithelial glycoprotein (RTE-Gp) was measured. By this method it was shown that only the lymph nodes that drain the site of immunization contained autoreactive B cells. Pretreatment with cyclosporine A (Cy-A) or with multiple injections of high doses of antigen in Freund's incomplete adjuvant markedly inhibited the development of disease to a subsequent nephritogenic challenge. In challenged high-dose-tolerant (HDT) rats the autoimmune response was only 5-10% of immunized nontolerant rats. This tolerance could not be transferred by lymphoid cells from Cy-A-treated rats, but could be transferred by lymphoid cells derived from the thymus or spleen of HDT rats. Thus a suppressor cell of thymic origin may be responsible for HDT. Transfer of affinity column-fractionated splenic T cells from HDT rats demonstrated that OX8- helper and OX8+ suppressor T cells are involved in the induction and suppression, respectively, of the autoimmune response in this experimental nephropathy.
de Heer
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Daha
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van Es
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D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004848:Epithelium / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007684:Kidney Tubules / Q000276:immunology*; D008297:Male; D009393:Nephritis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology*; D011919:Rats, Inbred Strains / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001323:Autoantibodies; D003524:Cyclosporins; D006023:Glycoproteins