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Natural killer cells in lung transplantation
  1. Daniel R Calabrese1,
  2. Lewis L Lanier2,3,
  3. John R Greenland1,4
  1. 1 Department of Medicine, University of California, San Francisco, California, USA
  2. 2 Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA
  3. 3 The Parker Institute for Cancer Immunotherapy, University of California San Francisco, San Francisco, California, USA
  4. 4 Medical Service, Veterans Affairs Health Care System, San Francisco, California, USA
  1. Correspondence to Dr John R Greenland, Department of Medicine, University of California, San Francisco CA 94121, USA; john.greenland{at}


Natural killer (NK) cells are innate lymphoid cells that have been increasingly recognised as important in lung allograft tolerance and immune defence. These cells evolved to recognise alterations in self through a diverse set of germline-encoded activating and inhibitory receptors and display a broad range of effector functions that play important roles in responding to infections, malignancies and allogeneic tissue. Here, we review NK cells, their diverse receptors and the mechanisms through which NK cells are postulated to mediate important lung transplant clinical outcomes. NK cells can promote tolerance, such as through the depletion of donor antigen-presenting cells. Alternatively, these cells can drive rejection through cytotoxic effects on allograft tissue recognised as ‘non-self’ or ‘stressed’, via killer cell immunoglobulin-like receptor (KIR) or NKG2D receptor ligation, respectively. NK cells likely mediate complement-independent antibody-mediated rejection of allografts though CD16A Fc receptor-dependent activation induced by graft-specific antibodies. Finally, NK cells play an important role in response to infections, particularly by mediating cytomegalovirus infection through the CD94/NKG2C receptor. Despite these sometimes-conflicting effects on allograft function, enumeration of NK cells may have an important role in diagnosing allograft dysfunction. While the effects of immunosuppression agents on NK cells may currently be largely unintentional, further understanding of NK cell biology in lung allograft recipients may allow these cells to serve as biomarkers of graft injury and as therapeutic targets.

  • innate immunity
  • lung transplantation
  • lymphocyte biology

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  • Contributors All individuals who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take responsibility for the content, including participation in the concept, design, writing or revision of the manuscript.

  • Funding This study was supported by Career development award IK2CX001034 from the VA Office of Research and Development Clinical Sciences Research & Development Service.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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