Blockade of TGF-beta signaling in T cells prevents the development of experimental glomerulonephritis

J Immunol. 2001 Feb 15;166(4):2818-23. doi: 10.4049/jimmunol.166.4.2818.


Anti-glomerular basement membrane (GBM) Ab-induced glomerulonephritis (GN) at late stage is thought to be mediated by T cells. However, signaling pathways of T cells that are involved in the development of anti-GBM Ab-induced GN are unclear. We have recently established transgenic mice expressing Smad7, an inhibitor of TGF-beta signaling, in mature T cells, where signaling by TGF-beta was blocked specifically in T cells. In this study, we showed that anti-GBM Ab-induced GN was suppressed in several measures in the transgenic mice including the severity of glomerular changes, proteinuria, renal function, and CD4 T cell infiltration into the glomeruli without down-regulation of CD62 ligand (CD62L) (L-selectin) expression on CD4 T cells. Furthermore, treatment with the soluble fusion protein of CD62L and IgG enhanced anti-GBM Ab-induced GN. These findings indicated that blockade of TGF-beta signaling in T cells prevented the development of anti-GBM Ab-induced GN. Because CD62L on T cells appears to be inhibitory for the development of anti-GBM Ab-induced GN, persistent expression of CD62L on CD4 T cells may explain, at least in part, the suppression of anti-GBM Ab-induced GN in the transgenic mice. Our findings suggest that the development of anti-GBM Ab-induced GN requires TGF-beta/Smad signaling in T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Antibodies / toxicity
  • Autoantibodies / metabolism
  • Autoantibodies / toxicity
  • Basement Membrane / immunology
  • Basement Membrane / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Complement C3 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / prevention & control*
  • Humans
  • Injections, Intravenous
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • L-Selectin / biosynthesis
  • L-Selectin / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Smad7 Protein
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / physiology*


  • Antibodies
  • Autoantibodies
  • Complement C3
  • DNA-Binding Proteins
  • SMAD7 protein, human
  • Smad7 Protein
  • Smad7 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • antiglomerular basement membrane antibody
  • L-Selectin