Donor Blood Monocytes but Not T or B Cells Facilitate Long-Term Allograft Survival After Total Lymphoid Irradiation1

Abstract

Infusion of donor monocytes facilitated graft prolongation via immune deviation.

Approaches to transplantation tolerance in humans

“…In our initial studies, we developed a model for tolerance induction in Lewis rat hosts given directly vascularized heterotopic heart transplants from MHC-mismatched ACI donors (26). The hosts were conditioned with 10 doses of TLI of 240 cGy each (total dose 2,400 cGy) starting on day 1 after transplantation and extending for a period of approximately 2 weeks (26).…”

“…The hosts were conditioned with 10 doses of TLI of 240 cGy each (total dose 2,400 cGy) starting on day 1 after transplantation and extending for a period of approximately 2 weeks (26). Rabbit ATG was administered in five divided doses during the first week, starting on day 0 (26).…”

“…The hosts were conditioned with 10 doses of TLI of 240 cGy each (total dose 2,400 cGy) starting on day 1 after transplantation and extending for a period of approximately 2 weeks (26). Rabbit ATG was administered in five divided doses during the first week, starting on day 0 (26). Although the combination of TLI and ATG administered after transplantation markedly prolonged graft survival, none of the hosts developed tolerance and all rejected their grafts within a 100-day observation period (26).…”

“…Although the combination of TLI and ATG administered after transplantation markedly prolonged graft survival, none of the hosts developed tolerance and all rejected their grafts within a 100-day observation period (26). A post-TLI infusion of PBMC or bone marrow cells from donors prolonged the acceptance of the heart allografts such that the large majority continued to beat for more than 150 days (26,27). Hosts with surviving donor grafts promptly rejected third-party grafts (26,27).…”

Upregulation of intragraft interleukin-10 by infusion of granulocyte colony-stimulating factor-mobilized donor leukocytes

“…Our previous studies using adult rat recipients prepared with a non-myeloablative post-transplant regimen of total lymphoid irradiation and anti-thymocyte globulin, showed that a single intravenous injection of donor blood after completion of the regimen facilitated tolerance to heart allografts and that the active cell subset in PBMCs was not lymphocytes but monocytes [13]. Intravenous injection of donor-type G-CSF-mobilized PBMCs used in the model also prolonged allograft survival [14].…”