NKT cells are important mediators of hepatic ischemia-reperfusion injury

Highlights

• Hepatic IRI worsens outcome in liver transplantation.

• T cells are important in hepatic IRI.

• These are tissue-resident rather than recruited T cells.

• NKT, but not conventional T or NK cells, are key mediators of hepatic IRI.

• Targeting NKT activation or their effector apparatus may offer therapeutic potential.

Abstract

Introduction

IRI results from the interruption then reinstatement of an organ's blood supply, and this poses a significant problem in liver transplantation and resectional surgery.

In this paper, we explore the role T cells play in the pathogenesis of this injury.

Materials & methods

We used an in vivo murine model of warm partial hepatic IRI, genetically-modified mice, in vivo antibody depletion, adoptive cell transfer and flow cytometry to determine which lymphocyte subsets contribute to pathology. Injury was assessed by measuring serum alanine aminotransfersase (ALT) and by histological examination of liver tissue sections.

Results

The absence of T cells (CD3εKO) is associated with significant protection from injury (p = 0.010). Through a strategy of antibody depletion it appears that NKT cells (p = 0.0025), rather than conventional T (CD4 + or CD8 +) (p = 0.11) cells that are the key mediators of injury.

Discussion

Our results indicate that tissue-resident NKT cells, but not other lymphocyte populations are responsible for the injury in hepatic IRI. Targeting the activation of NKT cells and/or their effector apparatus would be a novel approach in protecting the liver during transplantation and resection surgery; this may allow us to expand our current criteria for surgery.