Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

Abstract

The success of clinical lung transplantation is limited by allograft rejection. The role that passenger leukocytes play in lung graft alloimmunity is unclear. Here we tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of lung allograft rejection. Left lung allografts were orthotopically transplanted into single-haplotype full MHC-mismatched miniature swine (SLAac, class Iac/IIac) treated with cyclosporine for 12 days. Lung allografts were obtained from SLAad (class Iad/IIad) animals that underwent cytokine-mobilized hematopoietic stem cell transplant from SLAac (class Iac/IIac) donor animals; these chimeric animals achieved levels of >80% chimerism in the lymphoid and myeloid lineages prior to organ harvest. Animals in group 1 (n=2) received a lung allograft whose passenger leukocytes were MHC-matched to the recipient. Animals in group 2 (n=3) received a lung allograft whose passenger leukocytes were MHC-mismatched to the recipient. Lung allografts in group 1 survived on average 118 days (range 80-156) whereas lung allografts in group 2 survived on average 45 days (range 29-64, p=0.05). Animals in both groups showed in vitro evidence of donor-specific hyporesponsiveness by POD 30. Levels of circulating alloantibody were undetectable. Our data indicate that recipient-matching of passenger leukocytes significantly prolongs lung allograft survival. These studies may be applicable to clinical lung transplantation.