Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction

Kidney Int. 2010 Aug;78(4):351-62. doi: 10.1038/ki.2010.177. Epub 2010 Jun 16.


Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4(+) T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4(+) but not CD8(+) T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG(-/-) mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4(+) T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology*
  • Collagen / metabolism
  • Fibrosis / etiology*
  • Fibrosis / prevention & control
  • Homeodomain Proteins / genetics
  • Kidney Diseases / etiology*
  • Kidney Diseases / immunology
  • Lymphocyte Depletion / methods
  • Mice
  • Mice, Knockout
  • Ureteral Obstruction / complications*
  • Ureteral Obstruction / pathology


  • Homeodomain Proteins
  • RAG-1 protein
  • Collagen