Immunoregulation in experimental interstitial nephritis: immunization with renal tubular antigen in incomplete Freund's adjuvant induces major histocompatibility complex-restricted, OX8+ suppressor T cells which are antigen-specific and inhibit the expression of disease.
We utilized a model of experimental interstitial nephritis induced by renal tubular antigen in complete Freund's adjuvant to examine a mechanism of immunologic tolerance produced by priming immunization with tubular antigen in incomplete Freund's adjuvant. Brown Norway rats primed with tubular antigen in incomplete adjuvant do not develop significant nephritis after challenge with antigen in complete adjuvant, and this tolerance can be transferred to naive recipients with donor T cells. These T cells also specifically suppress a delayed-type hypersensitivity response to soluble tubular antigen in recipients immunized to produce disease. This suppression is MHC-restricted and is mediated by OX8+ T cells which bind antigen and bear idiotypes cross-reactive with those on antibodies eluted from the tubular basement membrane. Despite the suppression of histologic disease, tolerized animals were able to produce significant titers of antibodies to tubular basement membrane. Our findings demonstrate an additional strategy for altering the natural history of immune-mediated renal disease, and further refine the characterization of the suppressive effect produced by incomplete Freund's adjuvant.
C J
CJ
Kelly
M D
MD
Clayman
E G
EG
Neilson
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000502:physiology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005620:Freund's Adjuvant / Q000008:administration & dosage*; D006649:Histocompatibility Antigens / Q000235:genetics*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology; D008213:Lymphocyte Activation; D009395:Nephritis, Interstitial / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D000939:Epitopes; D006649:Histocompatibility Antigens; D007130:Immunoglobulin Idiotypes; C038353:histocompatibility antigens RT, rat; C035812:renal tubular antigen; D005620:Freund's Adjuvant