Rapid exchange of large numbers of donor- and host leukocytes after human liver transplantation

Abstract

After liver transplantation, the release of donor leukocytes into the host and the uptake of host leukocytes by the graft is one of the earliest immunologic interactions between donor and host. Using three-color flow cytometry, these interactions were investigated in eight patients from 5 min-24 h after receiving HLA unmatched liver grafts. Five minutes after reperfusion, 5.0 YO * 1.4 YO of all blood leukocytes in the host were of donor origin, decreasing to 1.1 % 0.8% after 24 h. Donor granulocytes preferentially disappeared from the host circulation, whereas no differences were found between NK-cells and various B-and T cell subpopulations. Furthermore, host granulocytes were preferentially retained in the donor liver. Thus, despite extensive pre-operative perfusion, more than lo9 donor leukocytes quickly leave the liver graft while host granulocytes preferentially accumulate there. A better understanding of the molecular mechanisms mediating these early interactions might help to develop new strategies for diagnosis and therapy of liver graft rejection.

Allosuppressive Donor CD4+CD25+ Regulatory T Cells Detach from the Graft and Circulate in Recipients after Liver Transplantation

“…To our knowledge, this study is the first to show the presence of CD4 ϩ CD25 ϩ Foxp3 ϩ T cells as passenger leukocytes in liver grafts. Following liver Tx, a substantial proportion of circulating leukocytes is of donor origin (28) and even higher in the case of graft-vs-host disease (32). In the first week after Tx, we have shown that up to 5% of the total CD4 ϩ CD25 ϩ CTLA4 ϩ T cell population were of donor origin (Fig.…”

“…Determination of HLA-A2 class 1 allele has previously been shown to be useful to distinguish between donor and recipients cells (27,28). A representative staining is shown in Fig.…”

Quantitative real‐time ARMS‐qPCR for mitochondrial DNA enables accurate detection of microchimerism in renal transplant recipients

“…Detection of donorspecific microchimerism after liver transplantation is thus not a surprising finding (1,53). Previous studies in recipients of HLA-unmatched liver grafts demonstrated that during the first 24 h after transplantation, up to 5% of all blood leukocytes in the host were of donor origin (52,53). In contrast, renal transplant recipients exhibited a far lower degree of blood microchimerism, and if detectable, it mainly occurred during the first four wk after kidney transplantation.…”

“…This is plausible because liver transplants are well known to contain large numbers of donor‐derived passenger immune cells (52). Detection of donor‐specific microchimerism after liver transplantation is thus not a surprising finding (1, 53). Previous studies in recipients of HLA‐unmatched liver grafts demonstrated that during the first 24 h after transplantation, up to 5% of all blood leukocytes in the host were of donor origin (52, 53).…”

Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance?

“…In one study, the mixing of donor and recipient immune cells appeared to peak approximately 90 min after reperfusion but persisted at 24 h in eight transplant recipients (17). Additional studies show donor NK cells in the host circulation and recipient NK cells within the graft shortly after revascularization (11,18). Importantly, in several rodent studies, passenger leukocytes were found to be involved in the phenomenon of spontaneous liver allograft tolerance, since irradiation of the donor liver, which resulted in the depletion of donor leukocytes, converted spontaneous acceptance to rejection (19)(20)(21).…”