ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Natural Killer Cell NKG2D Receptor Mediates Airway Cell Hypoxic Injury Through Recognition of Stress Molecules

T. Tsao1, E. Aminian1, A. Shemesh1, L. Tran1, P. Wang1, F. Deiter1, J. R. Greenland2, D. R. Calabrese1

1University of California, San Francisco, San Francisco, CA, 2Medicine, University of California, San Francisco, CA

Meeting: 2022 American Transplant Congress

Abstract number: 666

Keywords: Ischemia, Lung transplantation, Natural killer cells

Topic: Basic Science » Basic Science » 14 - Ischemia Reperfusion

Session Information

Session Name: Ischemia Reperfusion

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

 Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Primary graft dysfunction (PGD), the clinical syndrome of pulmonary hypoxia and reperfusion, occurs afer 1/3 of all lung transplants, and accounts for excess mortality. Previously, we showed a novel role of the Natural Killer (NK) cell stress receptor, NKG2D, in mouse models of PGD. We hypothesized that NKG2D stress molecules would be increased on hypoxic human airway cells and recognized by NK cells.

*Methods: Human airway epithelial cells were subjected to 6, 24, or 48 hours of hypoxia (n = 5, 1% oxygen) or normoxia (n = 5, 21% oxygen) (Fig. 1A). We measured transcripts of 8 human stress molecules (MICA, MICB, ULBP1-6) and hypoxia inducible factor 1a (HIF1A) by PCR and quantified fold change. NK cell cytotoxicity (n = 4) of normoxic or hypoxic airway epithelial cells was measured by flow cytometry after 24 hours of co-culture with primary human NK cells. NK cells were also treated with blocking anti-NKG2D monoclonal antibody before co-culture. Comparisons between conditions were made with the Mann Whitney U test.

*Results: HIF1A mRNA (Fig. 1B) was induced at 6 hours (p = 0.004) and 24 hours (p = 0.0001) but decreased at 48 hours (p = 0.001). All 8 human stress molecule transcripts (MICA, MICB, ULBP1-6) were increased within 48 hours of hypoxia. MICB (Fig. 1C) was increased by 1.4-fold (interquartile range [IQR] 1.38-1.46, p = 0.003) at 24 hours and 1.34-fold at 48 hours (IQR 1.26 – 1.37, p = 0.008). ULBP4 was increased 1.94-fold at 48 hours (IQR 1.72-2.1, p = 0.003, Fig. 1D). Figures 1E and 1F depict the design of co-culture experiments and representative flow cytometry cytotoxicity plots. We found that NK cells killed hypoxic epithelial cells at increased rates at any concentration when compared to the normoxia or anti-NKG2D groups (Figs. 1F & 1G). This was most evident at an effector to target ratio of 2:1, with 39% (IQR 38-40) cytotoxicity among hypoxic epithelial cells compared to anti-NKG2D NK cells (20%, IQR 19-20, p = 0.03) and normoxic epithelial cells (11%, IQR 10.8-11.1, p = 0.02). There was significantly increased area under the cytotoxicity curve for hypoxic epithelial cells compared to the normoxia (p = 0.02) or anti-NKG2D (p = 0.04) groups (Fig. 1H).

*Conclusions: Airway epithelial cell stress ligand transcripts are increased in response to hypoxia. Stress molecules are induced in a similar pattern to HIF1A but vary across time. NK cells kill hypoxic epithelial cells in an NKG2D receptor-dependent manner. A monoclonal antibody against the NKG2D receptor shows potential as a therapy for PGD.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Tsao T, Aminian E, Shemesh A, Tran L, Wang P, Deiter F, Greenland JR, Calabrese DR. Natural Killer Cell NKG2D Receptor Mediates Airway Cell Hypoxic Injury Through Recognition of Stress Molecules [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/natural-killer-cell-nkg2d-receptor-mediates-airway-cell-hypoxic-injury-through-recognition-of-stress-molecules/. Accessed May 30, 2025.

« Back to 2022 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences