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

• AKI: Mechanisms - Inflammation and AKI-CKD Transition
  November 08, 2019 | Location: 202, Walter E. Washington Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Bush, Errol L., Johns Hopkins, Baltimore, Maryland, United States

Errol L. Bush, MD



Errol L. Bush, M.D., FACS, is a thoracic surgeon and surgical director of the Advanced Lung Disease and Lung Transplant Program for the Johns Hopkins Comprehensive Transplant Center. Dr. Bush also serves as director of the Ex vivo Lung Perfusion Program (EVLP) at Johns Hopkins. EVLP is a novel therapy utilized outside of the body to resuscitate previously unsuitable donor lungs, thereby creating more suitable lungs for transplantation and effectively increasing donor supply. His clinical interests include surgical treatment of chronic and end stage lung diseases, as well as benign and malignant diseases and lesions of the chest. He is skilled in minimally invasive operations such as video-assisted thoracoscopic surgery (VATS), a type of thoracic surgery performed using a small video camera which is introduced into the patient's chest via a scope to treat lung cancers. Dr. Bush also has experience with Extracorporeal membrane oxygenation (ECMO), a technique of providing both cardiac and respiratory support oxygen to patients whose heart and lungs can no longer serve their function. His research interests include investigations of outcomes and health disparities related to lung cancer, lung transplant and ECMO patients.

• Hsu, Joshua, Johns Hopkins University, Baltimore, Maryland, United States

Joshua Hsu,

• Sadasivam, Mohanraj, Johns Hopkins University, Baltimore, Maryland, United States

Mohanraj Sadasivam,

• Hamad, Abdel, Johns Hopkins University, Baltimore, Maryland, United States

Abdel Hamad,

• Rabb, Hamid, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Hamid Rabb,

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