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Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response

Authors: Ivan Göcze, Katharina Ehehalt, Florian Zeman, Paloma Riquelme, Karin Pfister, Bernhard M. Graf, Thomas Bein, Edward K. Geissler, Piotr Kasprzak, Hans J. Schlitt, John A. Kellum, James A. Hutchinson, Elke Eggenhofer, Philipp Renner

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Basic science data suggest that acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI) is an inflammatory process involving the adaptive immune response. Little is known about the T-cell contribution in the very early phase, so we investigated if tubular cellular stress expressed by elevated cell cycle biomarkers is associated with early changes in circulating T-cell subsets, applying a bedside-to-bench approach.

Methods

Our observational pilot study included 20 consecutive patients undergoing endovascular aortic repair for aortic aneurysms affecting the renal arteries, thereby requiring brief kidney hypoperfusion and reperfusion. Clinical-grade flow cytometry-based immune monitoring of peripheral immune cell populations was conducted perioperatively and linked to tubular cell stress biomarkers ([TIMP-2]•[IGFBP7]) immediately after surgery. To confirm clinical results and prove T-cell infiltration in the kidney, we simulated tubular cellular injury in an established mouse model of mild renal IRI.

Results

A significant correlation between tubular cell injury and a peripheral decline of γδ T cells, but no other T-cell subpopulation, was discovered within the first 24 hours (r = 0.53; p = 0.022). Turning to a mouse model of kidney warm IRI, a similar decrease in circulating γδ T cells was found and concomitantly was associated with a 6.65-fold increase in γδ T cells (p = 0.002) in the kidney tissue without alterations in other T-cell subsets, consistent with our human data. In search of a mechanistic driver of IRI, we found that the damage-associated molecule high-mobility group box 1 protein HMGB1 was significantly elevated in the peripheral blood of clinical study subjects after tubular cell injury (p = 0.019). Correspondingly, HMGB1 RNA content was significantly elevated in the murine kidney.

Conclusions

Our investigation supports a hypothesis that γδ T cells are important in the very early phase of human AKI and should be considered when designing clinical trials aimed at preventing kidney damage.

Trial registration

ClinicalTrials.gov, NCT01915446. Registered on 5 Aug 2013.
Appendix
Available only for authorised users
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Metadata
Title
Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response
Authors
Ivan Göcze
Katharina Ehehalt
Florian Zeman
Paloma Riquelme
Karin Pfister
Bernhard M. Graf
Thomas Bein
Edward K. Geissler
Piotr Kasprzak
Hans J. Schlitt
John A. Kellum
James A. Hutchinson
Elke Eggenhofer
Philipp Renner
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2094-x

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