A role for regulatory T cells in renal acute kidney injury

Transpl Immunol. 2009 May;21(1):50-5. doi: 10.1016/j.trim.2009.02.003. Epub 2009 Feb 20.

Abstract

Ischemia reperfusion injury (IRI) is a potential contributor for the development of chronic allograft nephropathy. T cells are important mediators of injury, even in the absence of alloantigens. We performed a depletion of TCD4(+)CTLA4(+)Foxp3(+) cells with anti-CD25(PC61), a treatment with anti-GITR (DTA-1) and rat-IgG, followed by 45 min of ischemia and 24/72 h of reperfusion, and then analyzed blood urea, kidney histopathology and gene expression in kidneys by QReal Time PCR. After 24 h of reperfusion, depletion of TCD4(+)CTLA4(+)Foxp3(+) cells reached 30.3%(spleen) and 67.8%(lymph nodes). 72 h after reperfusion depletion reached 43.1%(spleen) and 90.22%(lymph nodes) and depleted animals presented with significantly poorer renal function, while DTA-1(anti-GITR)-treated ones showed a significant protection, all compared to serum urea from control group (IgG: 150.10+/-50.04; PC61: 187.23+/-31.38; DTA-1: 64.53+/-25.65, mg/dL, p<0.05). These data were corroborated by histopathology. We observed an increase of HO-1 expression in animals treated with DTA-1 at 72 h of reperfusion with significant differences. Thus, our results suggest that PC61(anti-CD25) mAb treatment is deleterious, while DTA-1(anti-GITR) mAb treatment presents a protective role in the renal IRI, indicating that some regulatory populations of T cells might have a role in IRI.

MeSH terms

  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / immunology*
  • Acute Kidney Injury / pathology
  • Animals
  • Blood Urea Nitrogen
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Gene Expression
  • Heme Oxygenase-1 / biosynthesis
  • Heme Oxygenase-1 / genetics
  • Kidney / immunology
  • Kidney / injuries
  • Kidney / pathology
  • Lymphocyte Depletion / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proliferating Cell Nuclear Antigen / biosynthesis
  • Proliferating Cell Nuclear Antigen / genetics
  • Reperfusion Injury / genetics
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Proliferating Cell Nuclear Antigen
  • Heme Oxygenase-1