1. Glomerulopathy Induced by Immunization with a Peptide Derived from the Goodpasture Antigen α3IV-NC1.
- Author
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Hopfer, Helmut, Hünemörder, Stefanie, Treder, Julia, Turner, Jan-Eric, Paust, Hans-Joachim, Meyer-Schwesinger, Catherine, Hopfer, Ulrike, Sachs, Marlies, Peters, Anett, Bucher-Kocaoglu, Biranda, Ahrens, Stefanie, Panzer, Ulf, and Mittrücker, Hans-Willi
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GLOMERULONEPHRITIS , *NEPHROTIC syndrome treatment , *IMMUNE response , *PEPTIDES , *T cells , *IMMUNIZATION , *IMMUNOLOGY - Abstract
Mouse experimental autoimmune glomerulonephritis, a model of human antiglomerular basement membrane disease, depends on both Ab and T cell responses to the Goodpasture Ag noncollagenous domain 1 of the α3-chain of type IV collagen (α3IV-NCl). The aim of our study was to further characterize the T cell-mediated immune response. Repeated immunization with mouse α3IV-NC1 caused fatal glomerulonephritis in DBA/1 mice. Although two immunizations were sufficient to generate high α3IV-NCl specific IgG titers, Ab and complement deposition along the glomerular basement membranes, and a nephrotic syndrome, two additional immunizations were needed to induce a necrotizing/crescentic glomerulonephritis. Ten days after the first immunization, α3IV-NCl-specific CD4+ cells producing TNF-α, IFN-γ, or IL-17A were detected in the spleen. With the emergence of necrotizing/crescentic glomerulonephritis, ~0.15% of renal CD4+ cells were specific for α3IV-NCl. Using peptides spanning the whole α3IV-NCl domain, three immunodominant T cell epitopes were identified. Immunization with these peptides did not lead to clinical signs of experimental autoimmune glomerulonephritis or necrotizing/crescentic glomerulonephritis. However, mice immunized with one of the peptides (STVKAGDLEKHSRC) developed circulating Abs against mouse α3IV-NCl first detected at 8 wk, and 50% of the mice showed mild proteinuria at 18-24 wk due to membranous glomerulopathy. Taken together, our results suggest that autoreactive T cells are able to induce the formation of pathologic autoantibodies. The quality and quantity of α3IV-NCl-specific Ab and T cell responses are critical for the phenotype of the glomerulonephritis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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