Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(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 a 3 chain of type IV collagen, alpha 3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha 3(IV)NC1; this peptide contain the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. in this study, we investigated die 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 mu g had no effect, a dose of 1000 mu g resulted in a moderate reduction in EAG severity, and a dose of 3000 mu g 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 alpha 3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders. (Am J Pathol 2009, 174:2202-2210; DOI: 10.2353/ajpath.2009.08104 1)