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Abstract: FR-OR025

Lung Double Negative (αβ+CD4-CD8-) T Cells Respond to AKI and Can Directly Protect from Lung Injury: A Protective Mediator During Kidney-Lung Cross-Talk?

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Bush, Errol L., Johns Hopkins, Baltimore, Maryland, United States
  • Hsu, Joshua, Johns Hopkins University, Baltimore, Maryland, United States
  • Sadasivam, Mohanraj, Johns Hopkins University, Baltimore, Maryland, United States
  • Hamad, Abdel, Johns Hopkins University, Baltimore, Maryland, United States
  • Rabb, Hamid, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Background

Kidney-lung cross talk during AKI contributes to the high mortality and reveals key interactions between lung and kidney. CD4-CD8- (double-negative; DN) αβ T cells have been recently described in kidney and rapidly respond to local ischemia reperfusion injury (IRI) with a protective anti-inflammatory cytokine profile, but the response to remote injury is unknown. We hypothesized that DN T cells serve a potential protective role as an immunologic mediator of kidney-lung crosstalk following remote as well as local injury.

Methods

B6 Wild type (WT) mice were subjected to IRI on either kidney or in lung by a established methods. Lymphocytes from lung was isolated and analysed by flow cytometry. H&E staining was performed with lung tissue to assess lung edema. Immunoblotting with cleaved caspase-3 was evaluated for apoptosis. To test the role for DN T cells in lung IRI, adoptive transfer of DN T cells prior to lung IRI was performed.

Results

Our data show that the frequency of lung DN T cell was significantly increased following both lung (39.1%) and kidney IRI (23.5%), p<0.05, compared to sham (10.7%). Immunoblotting of cleaved caspase-3 revealed higher levels of apoptosis at 3 and 6 hours of both renal and lung IRI. Evans blue extravasation demonstrated that adoptive transfer of DN T cells significantly decreased interstitial thickening and lung permeability (39.5 µg vs. 28 µg, p<0.05). Quantitative analysis of cleaved caspase-3 immunoblotting showed that DN T cell transfer attenuated cellular apoptosis (3.2 vs. 0.8, p<0.01). To assess the human relevance of lung DN T cells, lung samples were studied during implantation of lung transplants which were exposed to ischemia reperfusion, and DN T cells were also found in the human lungs (18.4% at ischemia, 39.2% at reperfusion).

Conclusion

These data demonstrate that DN T cells are a potential immunologic mediator of kidney-lung cross talk, and studies in lung IRI extend the role of DN T cells from kidney IRI to importance in lung injury as well. Further studies are needed to elucidate the mechanism of this potentially immunoregulatory response and human correlates

Funding

  • NIDDK Support