Autoimmunity against the Goodpasture antigen ?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 ?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 ?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? upon restimulation with ?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.Kidney International advance online publication, 21 March 2012; doi:10.1038/ki.2012.73.
