title: Characterization of the renal CD4+ T-cell response in experimental autoimmune glomerulonephritis.
abstract: Autoimmunity against the Goodpasture antigen α3IV-NC1 results in antiglomerular basement membrane glomerulonephritis. Although antibodies are central to the pathogenesis, there is good evidence for the participation of T cells in this disease. To define the contribution of T cells, we used the model of experimental autoimmune glomerulonephritis. Immunization of DBA/1 mice with α3IV-NC1 resulted in proteinuria, a biphasic course of the disease, and an eventual loss of kidney function. In the initial phase, the mice developed an α3IV-NC1-specific IgG response, had IgG deposition along the glomerular basement membrane, and steadily increased proteinuria, but only marginal signs of inflammation with limited leukocyte infiltration. After 9-13 weeks, mice proceeded to develop crescentic glomerulonephritis, extensive tubulointerstitial damage, and massive macrophage infiltration. T-cell infiltration was less pronounced, mostly confined to the interstitium, and T cells displayed an activated phenotype with a significant fraction of Th1 or Th17 CD4(+) T cells. Close examination revealed the presence of autoreactive T cells producing IFNγ upon restimulation with α3IV-NC1. Thus, our results suggest that accumulation of effector T cells, including autoreactive T cells, represents a critical step in the progression from mild glomerulonephritis, with limited glomerular damage, to severe crescentic glomerulonephritis accompanied by tubulointerstitial inflammation and loss of kidney function.
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Helmut
authors.initials: H
authors.lastname: Hopfer
authors.forename: Julia
authors.initials: J
authors.lastname: Holzer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hünemörder
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.forename: Marlies
authors.initials: M
authors.lastname: Sachs
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
mesh_terms: D000419:Albuminuria / Q000276:immunology; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000906:Antibodies / Q000097:blood; D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002633:Chemotaxis; D024141:Collagen Type IV; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D000906:Antibodies; D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D007371:Interferon-gamma