Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease

Lab Invest. 2008 Mar;88(3):284-92. doi: 10.1038/labinvest.3700715. Epub 2008 Jan 7.


One current theory for the emergence of glomerular nephritis implicates Th1-type cellular responses associated with delayed-type hypersensitivity, involving T cells and macrophages. Using a mouse model for progressive glomerulonephritis, we investigate the role of B and T cells in the pathogenesis of glomerular inflammation. Deletion of alpha3 chain of type IV collagen in mice (alpha3(IV) collagen null mice) results in GBM defects, glomerulonephritis and tubulointerstitial inflammation, fibrosis and significant immune infiltration including activated B- and T-lymphocytes. To evaluate the contribution of lymphocytes to the pathogenesis of glomerulonephritis and renal fibrosis, we generated mice that are deficient in both the alpha3(IV) collagen and Rag-1 (alpha3/Rag-1 DKO). Lymphocyte deficiency significantly reduces fibrosis in the renal interstitium, but ultrastructural GBM defects persist. Interestingly, glomerulonephritis in the double null mice persists at a similar level with comparable proteinuria. Here we demonstrate that despite the presence of B-cell and T-cells in the inflamed glomeruli, their deletion does not impede the emergence of glomerulonephritis but has a negative impact on the progression of renal interstitial fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / etiology
  • Albuminuria / physiopathology
  • Animals
  • B-Lymphocytes / physiology
  • Collagen Type IV / genetics
  • Creatine / analysis
  • Creatine / blood
  • Creatine / urine
  • Crosses, Genetic
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Fibrosis / etiology
  • Fibrosis / pathology
  • Gene Deletion
  • Glomerular Basement Membrane / pathology
  • Glomerular Basement Membrane / ultrastructure
  • Glomerulonephritis / etiology
  • Homeodomain Proteins / genetics
  • Immunohistochemistry
  • Lymphocytes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / physiopathology*
  • Nephritis, Hereditary / ultrastructure
  • Proteinuria / etiology
  • Proteinuria / physiopathology
  • Statistics as Topic
  • T-Lymphocytes / physiology
  • Time Factors


  • Collagen Type IV
  • Homeodomain Proteins
  • RAG-1 protein
  • Creatine