Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury

Kidney Int. 2009 Oct;76(7):717-29. doi: 10.1038/ki.2009.259. Epub 2009 Jul 22.


T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRbeta(+)CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury to the kidney. Using a murine model of ischemic acute kidney injury we found that there was a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys had increased numbers of TCRbeta(+)CD4(+) and TCRbeta(+)CD8(+) T cells with enhanced pro-inflammatory cytokine production. Treg depletion starting 1 day after ischemic injury using anti-CD25 antibodies increased renal tubular damage, reduced tubular proliferation at both time points, enhanced infiltrating T lymphocyte cytokine production at 3 days and TNF-alpha generation by TCRbeta(+)CD4(+) T cells at 10 days. In separate mice, infusion of CD4(+)CD25(+) Tregs 1 day after initial injury reduced INF-gamma production by TCRbeta(+)CD4(+) T cells at 3 days, improved repair and reduced cytokine generation at 10 days. Treg manipulation had minimal effect on neutrophil and macrophage infiltration; Treg depletion worsened mortality and serum creatinine, while Treg infusion had a late beneficial effect on serum creatinine in bilateral ischemia. Our study demonstrates that Tregs infiltrate ischemic-reperfused kidneys during the healing process promoting repair, likely through modulation of pro-inflammatory cytokine production of other T cell subsets. Treg targeting could be a novel therapeutic approach to enhance recovery from ischemic acute kidney injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Movement / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Forkhead Transcription Factors
  • Mice
  • Regeneration / physiology*
  • Reperfusion Injury / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Time Factors


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse