{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T11:56:11Z","timestamp":1774007771119,"version":"3.50.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"University of Cincinnati College of Medicine Internal Medicine Scholarly Training for Academic Research"},{"name":"University of Cincinnati Center for Clinical and Translational Science"},{"DOI":"10.13039\/100005160","name":"American Society of Transplantation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005160","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Burroughs Wellcome Fund Investigator in Infectious Disease"},{"name":"March of Dimes Foundation Ohio Collaborative for Prematurity Research"},{"DOI":"10.13039\/100000060","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI184537"],"award-info":[{"award-number":["R01AI184537"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Organ transplant recipients require continual immune-suppressive therapies to sustain allograft acceptance. Although medication nonadherence is a major cause of rejection, the mechanisms responsible for graft loss in this clinically relevant context among individuals with preceding graft acceptance remain uncertain. Here, we demonstrate that skin allograft acceptance in mice maintained with clinically relevant immune-suppressive therapies, tacrolimus and mycophenolate, sensitizes hypofunctional PD1hi graft-specific CD8+ T cells. Uninterrupted immune-suppressive therapy is required because drug discontinuation triggers allograft rejection, replicating the requirement for immune-suppressive therapy adherence in transplant recipients. Graft-specific CD8+ T cells in allograft-accepted mice show diminished effector differentiation and cytokine production, with reciprocally increased PD1 expression. Allograft acceptance\u2013induced PD1 expression is essential, as PDL1 blockade reinvigorates graft-specific CD8+ T cell activation with ensuing allograft rejection despite continual immune-suppressive therapy. Thus, PD1 sustained CD8+ T cell inhibition is essential for allograft acceptance maintained by tacrolimus plus mycophenolate. This necessity for PD1 in sustaining allograft acceptance explains the high rates of rejection in transplant recipients with cancer administered immune checkpoint inhibitors targeting PD1\/PDL1, highlighting shared immune suppression pathways exploited by tumor cells and current therapies for averting allograft rejection.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae007","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T14:56:51Z","timestamp":1737644211000},"page":"192-198","source":"Crossref","is-referenced-by-count":1,"title":["Immune suppression sustained allograft acceptance requires PD1 inhibition of CD8+ T cells"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-6025","authenticated-orcid":false,"given":"Hilary","family":"Miller-Handley","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Center for Inflammation and Tolerance, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"},{"name":"Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Harper","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for Inflammation and Tolerance, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-7759","authenticated-orcid":false,"given":"Giang","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for Inflammation and Tolerance, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-9745","authenticated-orcid":false,"given":"Lucien H","family":"Turner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for Inflammation and Tolerance, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2896-689X","authenticated-orcid":false,"given":"Tzu-Yu","family":"Shao","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for Inflammation and Tolerance, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail E","family":"Russi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Advanced Nutrition, Department of Pediatrics, Cincinnati Children\u2019s Hospital,University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-9302","authenticated-orcid":false,"given":"John J","family":"Erickson","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati College of Medicine, Cincinnati, OH, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-4421","authenticated-orcid":false,"given":"Mandy L","family":"Ford","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United 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