A role for regulatory T cells in renal acute kidney injury

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.

Regulatory T Cells in AKI

“…33 When PC61 was administered 24 hours before IRI (not far enough in advance to achieve maximal FoxP3 + Treg depletion at the time of injury), BUN levels and ATN were not different at 24 hours but significantly elevated compared with control antibody-treated mice at 72 hours after ischemia. 34 Furthermore, administration of the immunosuppressant mycophenolate mofetil in WT mice but not T cell-deficient mice inhibited recovery from renal IRI. 35 The impaired recovery from IRI in WT mice was associated with a dramatic reduction in Treg trafficking into the kidney.…”

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

“…4 Our group and others have demonstrated the role of different immune cell populations in kidney IRI. [5][6][7][8][9] Recently, an intimate connection between the intestine and the kidneys has been proposed. 10,11 Established data have already shown that modification of microbiota composition could affect the outcome of glomerulopathies, and recent data indicate that renal inflammation is associated with the production of uremic toxins by the intestine and with augments intestinal permeability, leading to the onset of systemic inflammation.…”

Role of Leukocytes in the Pathogenesis of Acute Kidney Injury

“…Reduction in numbers of Tregs predisposed mice to tubular necrosis, renal infl ammation and loss of function [37]. In other studies, Treg depletion prior to more severe ischemia also worsened renal injury measured at 72 h of reper fusion [38]. Th ese results suggest that enhancement of Treg numbers or function may be an eff ective preventative therapy for AKI.…”