CD4+ T Lymphocytes, especially Th2 cells, contribute to the progress of renal fibrosis

Am J Nephrol. 2012;36(4):386-96. doi: 10.1159/000343283. Epub 2012 Oct 9.


Background: Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated.

Methods: Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection.

Results: Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines.

Conclusion: In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy
  • Cell Differentiation / immunology
  • Disease Models, Animal
  • Fibrosis / immunology
  • Fibrosis / pathology
  • Flow Cytometry
  • Glomerulonephritis, IGA / immunology
  • Glomerulonephritis, IGA / pathology*
  • Humans
  • Kidney / immunology
  • Kidney / pathology*
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nephrosis, Lipoid / immunology
  • Nephrosis, Lipoid / pathology*
  • Renal Insufficiency, Chronic / immunology
  • Renal Insufficiency, Chronic / pathology*
  • Severity of Illness Index
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology*
  • Ureteral Obstruction / immunology
  • Ureteral Obstruction / pathology