A role for regulatory T cells in renal acute kidney injury.
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.
Monteiro
Rebecca M M
RM
Nephrology Division, Department of Medicine, Laboratory of Clinical and Experimental Immunology, Federal University of Sao Paulo UNIFESP-EPM, São Paulo, Brazil.
Camara
Niels O S
NO
Rodrigues
Mauricio M
MM
Tzelepis
Fanny
F
Damião
Marcio J
MJ
Cenedeze
Marcos A
MA
Teixeira
Vicente de Paula A
Vde P
dos Reis
Marlene A
MA
Pacheco-Silva
Alvaro
A
D058186:Acute Kidney Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001806:Blood Urea Nitrogen; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000276:immunology / Q000293:injuries / Q000473:pathology; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D051547:Heme Oxygenase-1