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Cross-dressed dendritic cells in liver transplant tolerance
Graft-infiltrating host cross-dressed dendritic cells (DCs) regulate antidonor T cell responses in mouse liver transplant tolerance. Top: Liver parenchymal cells, especially hepatocytes, release extracellular vesicles expressing donor MHC molecules that are acquired by host graft-infiltrating DCs (cross-dressing) that display upregulated programed death ligand 1 (PD-L1) and regulate responses of host alloreactive CD8+ T cells that express PD1 and TIM3. Bottom: Flow imaging of DCs harvested from the liver graft on postoperative day (POD) 7 and stained for CD11c, H-2Kb (donor), H-2Dk (host) and PD-L1. Colocalization of PD-L1 and MHC class I (Merge 1) on host DCs is shown. Two representative profiles from n = 103. After mouse allogeneic liver transplantation (1), approximately 60% of graft-infiltrating recipient DCs display donor MHC class I on POD 7, indicating cross-dressing. Cross-dressed DCs (CD-DCs) sorted from liver grafts express high levels of T cell inhibitory PD-L1. They also produce high levels of IL-10 and markedly suppress antidonor host T cell proliferation (2). Graft-infiltrating PD-L1hi CD-DCs may play a key role in the regulation of alloimmunity and in the induction of liver transplant tolerance (3). Original flow images published in Ono Y et al. Hepatology. 2018;67:1506. Reproduced with the permission of the publishers.
Authors: Yoshihiro Ono, Angelica Perez-Gutierrez, David A. Geller, MD, Angus W. Thomson, PhD, DSc
1. Yokota S, Ueki S, Ono Y, et al. Orthotopic mouse liver transplantation to study liver biology and allograft tolerance. Nat Protoc. 2016;11(7):1163–1174.
2. Ono Y, Perez-Gutierrez A, Nakao T, et al. Graft-infi ltrating PD-L1(hi) cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance. Hepatology. 2018;67(4):1499–1515.
3. Yokota S, Yoshida O, Ono Y, Geller DA, Thomson AW. Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance. Liver Transpl. 2016;22(4):536–546.