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Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet<jats:sup>+<\/jats:sup>Eomes<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells and CD16<jats:sup>bright<\/jats:sup>natural killer (NK) cells and an increase in putative tolerogenic CD141<jats:sup>+<\/jats:sup>CD163<jats:sup>+<\/jats:sup>DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-\u03b3<jats:sup>+<\/jats:sup>(IFN-\u03b3<jats:sup>+<\/jats:sup>) CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-\u03b3, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8<jats:sup>+<\/jats:sup>T cells, as well as attenuation of cytolytic T<jats:sub>H<\/jats:sub>1 effector genes and pathways among intragraft CD8<jats:sup>+<\/jats:sup>T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.<\/jats:p>","DOI":"10.1126\/scitranslmed.adf4287","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:59:07Z","timestamp":1697047147000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":37,"title":["Donor-derived regulatory dendritic cell infusion modulates effector CD8<sup>+<\/sup>T cell and NK cell responses after liver transplantation"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9317-4311","authenticated-orcid":true,"given":"Lillian M.","family":"Tran","sequence":"first","affiliation":[{"name":"Thomas E.\u00a0Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, 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