ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

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


  • 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

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.


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.


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).


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


  • NIDDK Support