The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice

FASEB J. 2003 May;17(8):860-8. doi: 10.1096/fj.02-0746com.


Anti-glomerular basement membrane (GBM) disease is a rapidly progressive glomerulonephritis (GN) resulting from autoimmunity against the Goodpasture antigen alpha3(IV)NC1. In addition to the well-characterized antibody contribution, a T helper 1 (Th1) response has been suspected as the culprit for glomerular injury. We induced anti-GBM disease in DBA/1, C57BL/6, AKR, and NOD mice with recombinant human alpha3(IV)NC1 to investigate the involvement of humoral and cellular autoimmunity. DBA/1 mice had crescentic GN 11 wk postimmunization with alpha3(IV)NC1. C57BL/6 and AKR mice developed a chronic disease course resulting in comparable kidney injury to DBA/1 mice within 6 months. NOD revealed only minor glomerular changes. The rapid course and the severity of the disease in DBA/1 mice can be explained by our immunological findings in their sera and splenocytes: 1) high antibody titers specific for the putative clinically relevant epitope of alpha3(IV)NC1 with Th1-type isotypes, and 2) a strong proliferative response and high amounts of the inflammatory cytokine IFN-gamma, secreted by splenocytes stimulated in vitro with alpha3(IV)NC1, with only low amounts of the anti-inflammatory cytokine IL-10. Our in vivo and in vitro results provide direct evidence that the balance between Th1 and Th2 responses associates with the outcome of anti-GBM disease in mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / pathology
  • Blotting, Western
  • Cell Line
  • Collagen Type IV / genetics
  • Collagen Type IV / immunology
  • Humans
  • Immunity, Cellular / immunology*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure
  • Male
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred NOD
  • Microscopy, Electron
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sclerosis
  • Severity of Illness Index
  • Species Specificity
  • Time Factors


  • Collagen Type IV
  • Recombinant Proteins