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- Title
Characterization of the renal CD4(+) T-cell response in experimental autoimmune glomerulonephritis.
- Authors
Hopfer H; Holzer J; Hünemörder S; Paust HJ; Sachs M; Meyer-Schwesinger C; Turner JE; Panzer U; Mittrücker HW
- Abstract
Autoimmunity against the Goodpasture antigen [alpha]3IV-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 [alpha]3IV-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 [alpha]3IV-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 IFN[gamma] upon restimulation with [alpha]3IV-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.
- Publication
Kidney International, 2012, Vol 82, Issue 1, p60
- ISSN
0085-2538
- Publication type
Journal Article
- DOI
10.1038/ki.2012.73