Cytokine Complex–expanded Natural Killer Cells Improve Allogeneic Lung Transplant Function via Depletion of Donor Dendritic Cells

Jungraithmayr, Wolfgang; Codarri, Laura; Bouchaud, Grégory; Krieg, Carsten; Boyman, Onur; Gyülvészi, Gábor; Becher, Burkhard; Weder, Walter; Münz, Christian

doi:10.1164/rccm.201209-1749oc

Cited by 40 publications

(38 citation statements)

References 46 publications

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“…In this study, the mouse NKG2D ligand Rae-1 had increased expression in allografts, overexpression of Rae-1 resulted in severe luminal fibrosis even in the absence of T or B cells and an antibody blocking NKG2D prevented this luminal fibrosis 51. Notably, these findings contrast with the study by Jungraithmayr et al ,26 where augmentation of NK cells by IL-15/IL-15Rα complex therapy before transplant resulted in depletion of APCs and protection from rejection pathology. Together these two studies suggest that magnitude, timing and context of NK cell responses may differentiate between protective versus destructive graft responses.…”

Section: Introductioncontrasting

confidence: 89%

Natural killer cells in lung transplantation

Calabrese

Lanier

Greenland

2018

Thorax

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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.

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Section: Introductioncontrasting

confidence: 89%

Natural killer cells in lung transplantation

Calabrese

Lanier

Greenland

2018

Thorax

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“…Direct allorecognition alone can result in acute rejection (AR), even without indirect mechanisms (2). Furthermore, depletion of donor immune cells from an organ prior to transplantation prevents rejection (3), and restoration re-establishes the alloresponse (4). It therefore appears that clinical outcome following transplantation is dependent on the early processes of recipient allorecognition of donor antigens.…”

Section: Introductionmentioning

confidence: 99%

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

Stone

Critchley

Major

et al. 2016

American Journal of Transplantation

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Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLPreduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.

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“…Further experiments indicated that the mechanism by which NK cells confer protection may be through removal of donor-derived dendritic cells from the allograft. These results provide an opportunity to consider whether preconditioning of lung recipients with regimens that augment NK cell reactivity may be beneficial for transplant outcomes (33).…”

Section: Mechanisms and Predictors Of Rejectionmentioning

confidence: 95%

Update in Lung Transplantation 2013

Todd

Christie

Palmer

2014

Am J Respir Crit Care Med

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Research in pulmonary transplantation is actively evolving in quality and scope to meet the challenges of a growing population of lung allograft recipients. In 2013, research groups leveraged large publicly available datasets in addition to multicenter research networks and single-center studies to make significant contributions to our knowledge and clinical care in the areas of donor use, clinical transplant outcomes, mechanisms of rejection, infectious complications, and chronic allograft dysfunction.

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Cytokine Complex–expanded Natural Killer Cells Improve Allogeneic Lung Transplant Function via Depletion of Donor Dendritic Cells

Abstract: These results suggest that NK cells favor allograft acceptance by depleting donor-derived DCs, which otherwise would prime alloreactive T-cell responses. Thus, conditioning regimens that augment NK-cell reactivity should be clinically explored to prepare lung allograft recipients.

Cited by 40 publications

References 46 publications

Natural killer cells in lung transplantation

Natural killer cells in lung transplantation

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

Update in Lung Transplantation 2013

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