Role of the T-cell receptor in kidney ischemia-reperfusion injury

V. Savransky, R. R. Molls, M. Burne-Taney, C. C. Chien, L. Racusen, H. Rabb

Research output: Contribution to journalArticlepeer-review

Abstract

T cells have been demonstrated to modulate ischemia-reperfusion injury (IRI) in kidney, lung, liver and intestine. The underlying mechanisms for T-cell engagement in IRI are unknown. We hypothesized that the T-cell receptor (TCR) plays a role in renal IRI, and examined the effects of TCR alpha/beta (αβ) and gamma/delta (γδ) deficiency on ischemic acute renal failure (ARF). TCR-specific deficiency in specific mice was confirmed by fluorescence-activated cell sorting analysis using monoclonal antibodies (Abs). IRI was induced by bilateral clamping of kidney pedicles for 30 min, followed by reperfusion. Serum creatinine and kidney histopathology were used to assess the severity of experimental ARF. TCR αβ-deficient mice were significantly protected from kidney dysfunction compared to wild-type (WT) littermates after IRI (P<0.05). Histologic analysis demonstrated a significant reduction in renal tubular injury in both TCR αβ- and γβ-deficient mice compared to WT mice postischemia. TCR αβ-deficient mice had reduced tumor necrosis factor-α and interleukin-6 protein expression in kidney tissue compared to WT mice at 24 h postischemia using a microbead-based protein detection platform. Relative protection from kidney IRI did not correlate with neutrophil and macrophage infiltration of kidney tissue. Thus, the TCR plays a direct but modest pathophysiological role in kidney IRI. These data suggest that alloantigen-independent activation in IRI can lead to engagement of antigen-specific molecules on T cells. Furthermore, given that the TCR is already a target for diagnostics and therapeutic strategies in immune diseases, these approaches can now be harnessed for IRI.

Original languageEnglish (US)
Pages (from-to)233-238
Number of pages6
JournalKidney international
Volume69
Issue number2
DOIs
StatePublished - Jan 2006

Keywords

  • Acute renal failure
  • Gene knockout mice
  • Ischemia/reperfusion injury
  • T-cell receptor

ASJC Scopus subject areas

  • Nephrology

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