BACKGROUND: The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory "congestion" of the liver graft, which is evidence of an early phase that we have termed "first cellular contact." METHODS: We have carried out by flow cytometry a prospective comparative study of the peak kinetics of lymphocyte subpopulations contained in: (a) peripheral blood and liver grafts at the time of multi-organ extraction from 14 brain-dead donors, (b) recipient peripheral blood before transplantation, and (c) recipient peripheral blood and liver grafts after (t=2 h) declamping and vascularization of the liver graft. RESULTS: Before transplantation, the liver grafts contained large numbers of natural killer (NK) and NK-like cells with early lymphocyte activation. Immediately after revascularization, there was an influx of recipient NK and NK-like cells into the liver. CONCLUSIONS: NK and CD3+CD56+ (NK-like) cells flooding into the liver graft immediately after revascularization could rapidly destroy allogeneic cells. However, spontaneous tolerance and the persistence of donor lymphocytes after orthotopic liver transplant could be a result of donor TCRalphabeta NK1.1 liver graft lymphocytes, which may be involved in the destruction of CD8+ T lymphocytes that would have received the apoptosis signal, and to NK and NK-like cell inhibition via inhibitory NK receptors. The decrease in gammadelta T lymphocytes in the two compartments suggests a mechanism of recirculation and capture in other lymphoid organs.
BACKGROUND: The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory "congestion" of the liver graft, which is evidence of an early phase that we have termed "first cellular contact." METHODS: We have carried out by flow cytometry a prospective comparative study of the peak kinetics of lymphocyte subpopulations contained in: (a) peripheral blood and liver grafts at the time of multi-organ extraction from 14 brain-dead donors, (b) recipient peripheral blood before transplantation, and (c) recipient peripheral blood and liver grafts after (t=2 h) declamping and vascularization of the liver graft. RESULTS: Before transplantation, the liver grafts contained large numbers of natural killer (NK) and NK-like cells with early lymphocyte activation. Immediately after revascularization, there was an influx of recipient NK and NK-like cells into the liver. CONCLUSIONS: NK and CD3+CD56+ (NK-like) cells flooding into the liver graft immediately after revascularization could rapidly destroy allogeneic cells. However, spontaneous tolerance and the persistence of donor lymphocytes after orthotopic liver transplant could be a result of donor TCRalphabeta NK1.1 liver graft lymphocytes, which may be involved in the destruction of CD8+ T lymphocytes that would have received the apoptosis signal, and to NK and NK-like cell inhibition via inhibitory NK receptors. The decrease in gammadelta T lymphocytes in the two compartments suggests a mechanism of recirculation and capture in other lymphoid organs.