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

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. EVLP‐reduced 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.

[1]  S. Keshavjee,et al.  Protein expression profiling predicts graft performance in clinical ex vivo lung perfusion. , 2015, Annals of surgery.

[2]  P. Dartevelle,et al.  Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience. , 2014, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[3]  J. Fildes,et al.  Mechanical removal of dendritic cell-generating non-classical monocytes via ex vivo lung perfusion. , 2014, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[4]  B. Becher,et al.  Cytokine complex-expanded natural killer cells improve allogeneic lung transplant function via depletion of donor dendritic cells. , 2013, American journal of respiratory and critical care medicine.

[5]  Marcelo Cypel,et al.  Experience with the first 50 ex vivo lung perfusions in clinical transplantation. , 2012, The Journal of thoracic and cardiovascular surgery.

[6]  Heinz Feldmann,et al.  A Hendra Virus G Glycoprotein Subunit Vaccine Protects African Green Monkeys from Nipah Virus Challenge , 2012, Science Translational Medicine.

[7]  G. Lang,et al.  Clinical Ex Vivo Lung Perfusion—Pushing the Limits , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  Marcelo Cypel,et al.  Normothermic ex vivo lung perfusion in clinical lung transplantation. , 2011, The New England journal of medicine.

[9]  Arthur S Slutsky,et al.  Functional Repair of Human Donor Lungs by IL-10 Gene Therapy , 2009, Science Translational Medicine.

[10]  S. Keshavjee,et al.  Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  Qiuming Liao,et al.  First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. , 2007, The Annals of thoracic surgery.

[12]  J. Kirby,et al.  The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  S. Steen,et al.  Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo. , 2003, The Annals of thoracic surgery.

[14]  R. Lechler,et al.  Pathways of allorecognition: implications for transplantation tolerance. , 2002, Transplant immunology.

[15]  S. Steen,et al.  Transplantation of lungs from a non-heart-beating donor , 2001, The Lancet.

[16]  R. Gill,et al.  CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II. , 2000, The Journal of clinical investigation.

[17]  K. Nadeau,et al.  Effects of explosive brain death on cytokine activation of peripheral organs in the rat. , 1998, Transplantation.

[18]  G. Rocker,et al.  The Systemic Inflammatory Response to Cardiopulmonary Bypass: Pathophysiological, Therapeutic, and Pharmacological Considerations , 1997 .

[19]  H. Schäfers,et al.  Allogeneic lymphocyte chimerism after clinical lung transplantation. , 1995, Transplant immunology.

[20]  H. Schäfers,et al.  Transmission of donor lymphocytes in clinical lung transplantation , 1994, Transplant international : official journal of the European Society for Organ Transplantation.

[21]  S. Steen,et al.  Safe lung preservation for twenty-four hours with Perfadex. , 1994, The Annals of thoracic surgery.

[22]  P. Morris,et al.  Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection , 1990, The Journal of experimental medicine.

[23]  R. Lechler,et al.  Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells , 1982, The Journal of experimental medicine.