Graft‐infiltrating PD‐L1hi cross‐dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance

• DOI: 10.1002/hep.29529
• Publication Date: 2017-09-18T14:13:01Z
• Authors: Yoshihiro Ono; Angelica Perez‐Gu...; Toshimasa Nakao; Helong Dai; Geoffrey Camirand; Osamu Yoshida; Shinichiro Yokota; Donna Beer Stolz; Mark A. Ross; Adrian E. Morelli; David A. Geller; Angus W. Thomson
• Keywords: Immunologic Tolerance

Although a key role of cross‐dressing has been established in immunity to viral infection and more recently the instigation transplant rejection, its tolerance is unclear. We investigated intragraft dendritic cells (DCs) mouse major histocompatibility complex (MHC)‐mismatched liver that occurs without therapeutic immunosuppression. donor interstitial DCs diminished rapidly after transplantation, they were replaced by host peaked on postoperative day (POD) 7 persisted indefinitely. Approximately 60% these recipient displayed MHC class I, indicating cross‐dressing. By contrast, only very minor fraction (0%‐2%) cross‐dressed (CD‐DCs) was evident spleen. CD‐DCs sorted from grafts expressed much higher levels T cell inhibitory programed death ligand 1 (PD‐L1) high interleukin‐10 compared with non–CD‐DCs (nCD‐DCs) isolated graft. Concomitantly, incidences protein (PD‐1)hi immunoglobulin mucin domain containing 3 (TIM‐3)+ exhausted graft‐infiltrating CD8+ observed. Unlike nCD‐DCs, failed stimulate proliferation allogeneic but markedly suppressed antidonor proliferation. less allografts DNAX‐activating 12 kDa (DAP12)−/− donors rejected acutely. Conclusion: These findings suggest PD‐L1hi may play regulation alloimmunity induction tolerance. (Hepatology 2018;67:1499‐1515)