Donor-derived regulatory dendritic cell infusion results in host cell cross-dressing and T cell subset changes in prospective living donor liver transplant recipients.

Donor-derived regulatory dendritic cell infusion results in host cell cross-dressing and T cell subset changes in prospective living donor liver transplant recipients.
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DOI:
10.1111/ajt.16393
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发表时间:
2021-07
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Thomson AW
Thomson AW
中科院分区:
其他
文献类型:
--
作者:
Macedo C;Tran LM;Zahorchak AF;Dai H;Gu X;Ravichandran R;Mohanakumar T;Elinoff B;Zeevi A;Styn MA;Humar A;Lakkis FG;Metes DM;Thomson AW

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Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand-1 (PD-L1):CD86 ratios, high IL-10/no IL-12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5–10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD-L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and “cross-dressing” of host DCs in blood and lymph nodes. PD-L1 co-localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T-bethiEomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hiCD127−Foxp3+): T-bethiEomeshi CD8+ T cell ratios increased. Thus, donor-derived DCreg infusion may induce systemic changes in host antigen-presenting cells and T cells potentially conducive to modulated anti-donor immune reactivity at the time of transplant.
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