Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in established experimental autoimmune glomerulonephritis.
Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000 microg resulted in a moderate reduction in EAG severity, and a dose of 3000 microg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders.
Reynolds
John
J
Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, Du Cane Rd., London W12 ONN, UK. john.reynolds@imperial.ac.uk
Abbott
Danielle S
DS
Karegli
Julieta
J
Evans
David J
DJ
Pusey
Charles D
CD
D000281:Administration, Intranasal; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D015153:Blotting, Western; D024141:Collagen Type IV / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D001324:Autoantigens; D024141:Collagen Type IV; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C057112:type IV collagen alpha3 chain