A role for regulatory T cells in renal acute kidney injury

• Published in: Transplant immunology 2009-05, Vol.21 (1), p.50-55
• Main Authors: Monteiro, Rebecca M.M, Camara, Niels O.S, Rodrigues, Mauricio M, Tzelepis, Fanny, Damião, Marcio J, Cenedeze, Marcos A, Teixeira, Vicente de Paula A, dos Reis, Marlene A, Pacheco-Silva, Alvaro
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - genetics; Acute Kidney Injury - immunology; Acute Kidney Injury - pathology; Acute renal failure; Allergy and Immunology; Animals; Anti-CD25 (PC61); Anti-GITR (DTA-1); Blood Urea Nitrogen; Flow Cytometry; Forkhead Transcription Factors - biosynthesis; Forkhead Transcription Factors - genetics; Gene Expression; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - genetics; HO-1; Ischemia and reperfusion injury; 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; TCD4 + lymphocytes
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2009.02.003

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.