{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:14:35Z","timestamp":1789568075487,"version":"build-2803163510"},"reference-count":104,"publisher":"Portland Press Ltd.","issue":"21","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:p>Allogeneic haematopoietic stem cell transplantation (alloHSCT) is a curative treatment for haematological malignancies. AlloHSCT aims to generate graft-versus-leukaemia immunity, where donor T cells eliminate residual malignant cells. However, graft-versus-host disease (GVHD), where donor T cells attack recipient tissues, is a common and often fatal side effect. Post-transplant cyclophosphamide (PTCy) can reduce GVHD, but the cellular mechanisms through which this occurs are not fully understood, and high doses may be associated with toxicity. This study aimed to determine whether lower doses of PTCy can reduce GVHD and to examine the effects of PTCy doses on human (h) immune cell subsets, T cell exhaustion, and histological GVHD in a humanised mouse model. NOD-scid-IL2R\u03b3null mice were injected with 2 \u00d7 107 human peripheral blood mononuclear cells on day 0, cyclophosphamide (10, 25 or 33 mg\/kg) or control diluent on days 3 and 4 and monitored for GVHD development at early and late time points. Low-dose PTCy (10 mg\/kg) abrogated clinical signs of GVHD with comparable efficacy to high-dose PTCy (33 mg\/kg), delaying GVHD onset and prolonging mouse survival. Proportions of hPD-1+ hCD4+ and hPD-1+hCD8+ T cells were increased with low-dose PTCy but not higher doses, while hPD-1+ hTreg proportions were increased by all PTCy doses. Exhausted hPD-1+hLAG3+hCD8+ T cell proportions were increased with high-dose PTCy, but not lower doses. This study indicates that low-dose PTCy reduces GVHD with similar efficacy to that of high-dose PTCy, but this appears to be associated with differing cellular mechanisms of action.<\/jats:p>","DOI":"10.1042\/cs20257272","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T17:07:15Z","timestamp":1762967235000},"page":"1261-1285","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low- and high-dose post-transplant cyclophosphamide attenuates graft-versus-host disease with distinct effects on PD-1+ T cell subsets"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9214-0742","authenticated-orcid":false,"given":"Chloe","family":"Sligar","sequence":"first","affiliation":[{"name":"1Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4212-3432","authenticated-orcid":false,"given":"Miles J.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"1Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0625-3183","authenticated-orcid":false,"given":"Amal","family":"Elhage","sequence":"additional","affiliation":[{"name":"1Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-686X","authenticated-orcid":false,"given":"Ronald","family":"Sluyter","sequence":"additional","affiliation":[{"name":"1Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6242-3944","authenticated-orcid":false,"given":"Debbie","family":"Watson","sequence":"additional","affiliation":[{"name":"1Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"2025111212071284900_CS-2025-7272C1","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMra052638","article-title":"Hematopoietic stem-cell transplantation","volume":"354","author":"Copelan","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025111212071284900_CS-2025-7272C2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3389\/fimmu.2017.00496","article-title":"Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia","volume":"8","author":"Dickinson","year":"2017","journal-title":"Front. Immunol."},{"key":"2025111212071284900_CS-2025-7272C3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","article-title":"Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors","volume":"18","author":"Glucksberg","year":"1974","journal-title":"Transplantation"},{"key":"2025111212071284900_CS-2025-7272C4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1182\/blood-2011-06-364265","article-title":"Risk factors for acute GVHD and survival after hematopoietic cell transplantation","volume":"119","author":"Jagasia","year":"2012","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/pmj.78.919.257","article-title":"Non-infectious pulmonary complications after bone marrow transplantation","volume":"78","author":"Khurshid","year":"2002","journal-title":"Postgrad. Med. J."},{"key":"2025111212071284900_CS-2025-7272C6","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3006960","article-title":"Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide","volume":"5","author":"Kanakry","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"2025111212071284900_CS-2025-7272C7","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1200\/JCO.2013.54.0625","article-title":"Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning","volume":"32","author":"Kanakry","year":"2014","journal-title":"J. Clin. Oncol"},{"key":"2025111212071284900_CS-2025-7272C8","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1182\/blood-2009-11-251595","article-title":"High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease","volume":"115","author":"Luznik","year":"2010","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12026-009-8139-0","article-title":"High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation","volume":"47","author":"Luznik","year":"2010","journal-title":"Immunol. Res."},{"key":"2025111212071284900_CS-2025-7272C10","article-title":"Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide","volume":"3 Suppl 2","author":"Munchel","year":"2011","journal-title":"Pediatr. Rep."},{"key":"2025111212071284900_CS-2025-7272C11","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.jtct.2021.07.023","article-title":"Increased infections and delayed CD4+ T cell but faster B cell immune reconstitution after post-transplantation cyclophosphamide compared to conventional GVHD prophylaxis in allogeneic transplantation","volume":"27","author":"Khimani","year":"2021","journal-title":"Transplant. Cell. Ther"},{"key":"2025111212071284900_CS-2025-7272C12","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1171","article-title":"High-dose post-transplant cyclophosphamide impairs \u03b3\u03b4 T-cell reconstitution after haploidentical haematopoietic stem cell transplantation using low-dose antithymocyte globulin and peripheral blood stem cell graft","volume":"9","author":"Stocker","year":"2020","journal-title":"Clin. Transl. Immunology"},{"key":"2025111212071284900_CS-2025-7272C13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-022-01287-3","article-title":"Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant","volume":"15","author":"Zhao","year":"2022","journal-title":"J. Hematol. Oncol"},{"key":"2025111212071284900_CS-2025-7272C14","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","article-title":"Cyclophosphamide and cancer: golden anniversary","volume":"6","author":"Emadi","year":"2009","journal-title":"Nat. Rev. Clin. Oncol"},{"key":"2025111212071284900_CS-2025-7272C15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jaccao.2021.02.011","article-title":"Early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation","volume":"3","author":"Dul\u00e9ry","year":"2021","journal-title":"JACC CardioOncol."},{"key":"2025111212071284900_CS-2025-7272C16","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1182\/blood-2002-06-1860","article-title":"Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation","volume":"101","author":"McDonald","year":"2003","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C17","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/jnci\/87.7.524","article-title":"Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin\u2019s lymphoma","volume":"87","author":"Travis","year":"1995","journal-title":"JNCI Journal of the National Cancer Institute"},{"key":"2025111212071284900_CS-2025-7272C18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s11096-015-0069-4","article-title":"Secondary acute myeloid leukemia arising early after cyclophosphamide treatment","volume":"37","author":"Koklu","year":"2015","journal-title":"Int. J. Clin. Pharm."},{"key":"2025111212071284900_CS-2025-7272C19","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1172\/JCI124218","article-title":"Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression","volume":"129","author":"Wachsmuth","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2025111212071284900_CS-2025-7272C20","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2017.1356152","article-title":"Low-dose post-transplant cyclophosphamide can mitigate GVHD and enhance the G-CSF\/ATG induced GVHD protective activity and improve haploidentical transplant outcomes","volume":"6","author":"Wang","year":"2017","journal-title":"Oncoimmunology"},{"key":"2025111212071284900_CS-2025-7272C21","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-019-0781-y","article-title":"Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients","volume":"12","author":"Wang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"2025111212071284900_CS-2025-7272C22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41409-022-01908-y","article-title":"Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies","volume":"58","author":"Dul\u00e9ry","year":"2023","journal-title":"Bone Marrow Transplant."},{"key":"2025111212071284900_CS-2025-7272C23","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.4049\/jimmunol.145.5.1303","article-title":"Sequential mechanisms of cyclophosphamide-induced skin allograft tolerance including the intrathymic clonal deletion followed by late breakdown of the clonal deletion","volume":"145","author":"Eto","year":"1990","journal-title":"J. Immunol."},{"key":"2025111212071284900_CS-2025-7272C24","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1182\/blood-2013-10-525873","article-title":"Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice","volume":"124","author":"Ganguly","year":"2014","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C25","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025111212071284900_CS-2025-7272C26","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2025111212071284900_CS-2025-7272C27","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.3389\/fimmu.2018.02374","article-title":"Inhibitory receptors and pathways of lymphocytes: the role of PD-1 in Treg development and their involvement in autoimmunity onset and cancer progression","volume":"9","author":"Gianchecchi","year":"2018","journal-title":"Front. Immunol."},{"key":"2025111212071284900_CS-2025-7272C28","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/s41590-020-0801-7","article-title":"PD-1+ Treg cells: A foe in cancer immunotherapy?","volume":"21","author":"Aksoylar","year":"2020","journal-title":"Nat. Immunol"},{"key":"2025111212071284900_CS-2025-7272C29","first-page":"269","article-title":"LAG-3 in cancer immunotherapy","volume":"344","author":"Goldberg","year":"2011","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2025111212071284900_CS-2025-7272C30","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.cell.2015.10.054","article-title":"Snapshot: T cell exhaustion","volume":"163","author":"Pauken","year":"2015","journal-title":"Cell"},{"key":"2025111212071284900_CS-2025-7272C31","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1038\/s41467-020-17991-y","article-title":"T cell exhaustion and a failure in antigen presentation drive resistance to the graft-versus-leukemia effect","volume":"11","author":"Zhou","year":"2020","journal-title":"Nat. Commun."},{"key":"2025111212071284900_CS-2025-7272C32","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.bbmt.2018.03.030","article-title":"Reversal of T cell exhaustion by the first donor lymphocyte infusion is associated with the persistently effective antileukemic responses in patients with relapsed AML after allo-HSCT","volume":"24","author":"Liu","year":"2018","journal-title":"Biol. Blood Marrow Transplant"},{"key":"2025111212071284900_CS-2025-7272C33","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.clim.2018.02.009","article-title":"T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation","volume":"190","author":"Liu","year":"2018","journal-title":"Clin. Immunol."},{"key":"2025111212071284900_CS-2025-7272C34","doi-asserted-by":"crossref","first-page":"956","DOI":"10.3324\/haematol.2008.003103","article-title":"Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab","volume":"94","author":"Matthews","year":"2009","journal-title":"Haematologica"},{"key":"2025111212071284900_CS-2025-7272C35","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1182\/blood.V99.10.3493","article-title":"The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality","volume":"99","author":"Taylor","year":"2002","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C36","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nature06306","article-title":"The inhibitory cytokine IL-35 contributes to regulatory T-cell function","volume":"450","author":"Collison","year":"2007","journal-title":"Nature"},{"key":"2025111212071284900_CS-2025-7272C37","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ni.2496","article-title":"The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood","volume":"14","author":"Sage","year":"2013","journal-title":"Nat. Immunol."},{"key":"2025111212071284900_CS-2025-7272C38","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1182\/bloodadvances.2019000134","article-title":"PTCy ameliorates GVHD by restoring regulatory and effector T-cell homeostasis in recipients with PD-1 blockade","volume":"3","author":"Ikegawa","year":"2019","journal-title":"Blood Adv."},{"key":"2025111212071284900_CS-2025-7272C39","doi-asserted-by":"crossref","first-page":"15211","DOI":"10.1038\/s41598-019-51674-z","article-title":"Cage aggression in group-housed laboratory male mice: An international data crowdsourcing project","volume":"9","author":"Lidster","year":"2019","journal-title":"Sci. Rep."},{"key":"2025111212071284900_CS-2025-7272C40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s11302-019-09651-8","article-title":"Altered donor P2X7 activity in human leukocytes correlates with P2RX7 genotype but does not affect the development of graft-versus-host disease in humanised mice","volume":"15","author":"Adhikary","year":"2019","journal-title":"Purinergic Signal."},{"key":"2025111212071284900_CS-2025-7272C41","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.2337\/db19-0525","article-title":"Low-dose interleukin-2 combined with rapamycin led to an expansion of CD4+CD25+FOXP3+ regulatory T cells and prolonged human islet allograft survival in humanized mice","volume":"69","author":"Hu","year":"2020","journal-title":"Diabetes"},{"key":"2025111212071284900_CS-2025-7272C42","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2025111212071284900_CS-2025-7272C43","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1042\/CS20191086","article-title":"Increased P2X7 expression in the gastrointestinal tract and skin in a humanised mouse model of graft-versus-host disease","volume":"134","author":"Cuthbertson","year":"2020","journal-title":"Clin. Sci"},{"key":"2025111212071284900_CS-2025-7272C44","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/imm.13374","article-title":"Post-transplant cyclophosphamide limits reactive donor T cells and delays the development of graft-versus-host disease in a humanized mouse model","volume":"164","author":"Adhikary","year":"2021","journal-title":"Immunology"},{"key":"2025111212071284900_CS-2025-7272C45","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1136\/practneurol-2019-002247","article-title":"Preserving fertility: using cyclophosphamide and other cytotoxics in young people","volume":"20","author":"Ledingham","year":"2020","journal-title":"Pract Neurol (Fort Wash Pa)"},{"key":"2025111212071284900_CS-2025-7272C46","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.trim.2019.02.003","article-title":"Increased splenic human CD4+:CD8+ T cell ratios, serum human interferon-\u03b3 and intestinal human interleukin-17 are associated with clinical graft-versus-host disease in humanized mice","volume":"54","author":"Geraghty","year":"2019","journal-title":"Transpl. Immunol"},{"key":"2025111212071284900_CS-2025-7272C47","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/imcb.12652","article-title":"Tocilizumab increases regulatory T cells, reduces natural killer cells and delays graft-versus-host disease development in humanized mice treated with post-transplant cyclophosphamide","volume":"101","author":"Sligar","year":"2023","journal-title":"Immunol. Cell Biol."},{"key":"2025111212071284900_CS-2025-7272C48","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/pbc.25347","article-title":"Impact of very early CD4(+) \/CD8(+) T cell counts on the occurrence of acute graft-versus-host disease and NK cell counts on outcome after pediatric allogeneic hematopoietic stem cell transplantation","volume":"62","author":"Huttunen","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"2025111212071284900_CS-2025-7272C49","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00277-017-2999-5","article-title":"Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines","volume":"96","author":"Budde","year":"2017","journal-title":"Ann. Hematol."},{"key":"2025111212071284900_CS-2025-7272C50","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases","volume":"155","author":"Sakaguchi","year":"1995","journal-title":"J. Immunol."},{"key":"2025111212071284900_CS-2025-7272C51","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/cmi.2016.30","article-title":"Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions","volume":"14","author":"Gu","year":"2017","journal-title":"Cell. Mol. Immunol."},{"key":"2025111212071284900_CS-2025-7272C52","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1182\/bloodadvances.2016002980","article-title":"Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT","volume":"1","author":"Gartlan","year":"2017","journal-title":"Blood Adv."},{"key":"2025111212071284900_CS-2025-7272C53","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1182\/blood.V90.8.3204","article-title":"Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines","volume":"90","author":"Hill","year":"1997","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C54","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.4049\/jimmunol.1501020","article-title":"T-bet promotes acute graft-versus-host disease by regulating recipient hematopoietic cells in mice","volume":"196","author":"Fu","year":"2016","journal-title":"J. Immunol."},{"key":"2025111212071284900_CS-2025-7272C55","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1182\/blood-2015-01-622662","article-title":"Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects","volume":"126","author":"Gartlan","year":"2015","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C56","doi-asserted-by":"crossref","DOI":"10.1126\/science.abi9591","article-title":"KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19","volume":"376","author":"Li","year":"2022","journal-title":"Science"},{"key":"2025111212071284900_CS-2025-7272C57","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41590-024-02062-x","article-title":"Differential roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses","volume":"26","author":"Chen","year":"2025","journal-title":"Nat. Immunol"},{"key":"2025111212071284900_CS-2025-7272C58","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ni.3298","article-title":"The burgeoning family of unconventional T cells","volume":"16","author":"Godfrey","year":"2015","journal-title":"Nat. Immunol."},{"key":"2025111212071284900_CS-2025-7272C59","article-title":"\u03b3\u03b4 T cells may aggravate acute graft-versus-host disease through CXCR4 signaling after allogeneic hematopoietic transplantation","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Immunol."},{"key":"2025111212071284900_CS-2025-7272C60","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1084\/jem.189.7.1073","article-title":"Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease","volume":"189","author":"Zeng","year":"1999","journal-title":"J. Exp. Med."},{"key":"2025111212071284900_CS-2025-7272C61","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.4049\/jimmunol.167.4.2087","article-title":"Predominance of NK1.1+TCR alpha beta+ or DX5+TCR alpha beta+ T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: \u201cnatural suppressor\u201d cells","volume":"167","author":"Lan","year":"2001","journal-title":"J. Immunol."},{"key":"2025111212071284900_CS-2025-7272C62","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1042\/CS20201352","article-title":"P2X7 receptor antagonism increases regulatory T cells and reduces clinical and histological graft-versus-host disease in a humanised mouse model","volume":"135","author":"Cuthbertson","year":"2021","journal-title":"Clin. Sci"},{"key":"2025111212071284900_CS-2025-7272C63","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1182\/blood-2009-05-222190","article-title":"NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects","volume":"115","author":"Olson","year":"2010","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-023-00438-1","article-title":"Acute graft-versus-host disease","volume":"9","author":"Malard","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2025111212071284900_CS-2025-7272C65","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0133216","article-title":"Humanized chronic graft-versus-host disease in NOD-SCID il2r\u03b3-\/- (NSG) mice with G-CSF-mobilized peripheral blood mononuclear cells following cyclophosphamide and total body irradiation","volume":"10","author":"Fujii","year":"2015","journal-title":"PLOS ONE"},{"key":"2025111212071284900_CS-2025-7272C66","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.3389\/fimmu.2019.02668","article-title":"Mechanisms of graft-versus-host disease prevention by post-transplantation cyclophosphamide: an evolving understanding","volume":"10","author":"Nunes","year":"2019","journal-title":"Front. Immunol."},{"key":"2025111212071284900_CS-2025-7272C67","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25031775","article-title":"Post-transplant cyclophosphamide combined with Brilliant Blue G reduces graft-versus-host disease without compromising graft-versus-leukaemia immunity in humanised mice","volume":"25","author":"Cuthbertson","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"2025111212071284900_CS-2025-7272C68","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bbmt.2019.09.030","article-title":"Optimized timing of post-transplantation cyclophosphamide in MHC-haploidentical murine hematopoietic cell transplantation","volume":"26","author":"Wachsmuth","year":"2020","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025111212071284900_CS-2025-7272C69","article-title":"Partially replacing cyclophosphamide with bendamustine in combination with cyclosporine A improves survival and reduces xenogeneic graft-versus-host-disease","volume":"13","author":"Gilman","year":"2022","journal-title":"Front. Immunol."},{"key":"2025111212071284900_CS-2025-7272C70","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0192-0561(90)90056-S","article-title":"Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice","volume":"12","author":"Pukhalsky","year":"1990","journal-title":"Int. J. Immunopharmacol."},{"key":"2025111212071284900_CS-2025-7272C71","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.immuni.2024.11.026","article-title":"Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion","volume":"58","author":"Waibl Polania","year":"2025","journal-title":"Immunity"},{"key":"2025111212071284900_CS-2025-7272C72","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.immuni.2018.12.021","article-title":"Intratumoral Tcf1+PD-1+CD8+ T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy","volume":"50","author":"Siddiqui","year":"2019","journal-title":"Immunity"},{"key":"2025111212071284900_CS-2025-7272C73","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1073\/pnas.1718217115","article-title":"Role of PD-1 during effector CD8 T cell differentiation","volume":"115","author":"Ahn","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2025111212071284900_CS-2025-7272C74","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41392-024-02000-1","article-title":"PD-1 and LAG-3: synergistic fostering of T cell exhaustion","volume":"9","author":"Hofmann","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"2025111212071284900_CS-2025-7272C75","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1172\/JCI96107","article-title":"PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation","volume":"128","author":"Petrelli","year":"2018","journal-title":"J. Clin. Invest"},{"key":"2025111212071284900_CS-2025-7272C76","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.142513","article-title":"PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells","volume":"6","author":"Balan\u00e7a","year":"2021","journal-title":"JCI Insight"},{"key":"2025111212071284900_CS-2025-7272C77","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"2025111212071284900_CS-2025-7272C78","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"2025111212071284900_CS-2025-7272C79","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","article-title":"T cell factor 1-expressing memory-like CD8+ T cells sustain the immune response to chronic viral infections","volume":"45","author":"Utzschneider","year":"2016","journal-title":"Immunity"},{"key":"2025111212071284900_CS-2025-7272C80","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1196\/annals.1447.009","article-title":"Humanized mice for the study of type 1 diabetes and beta cell function","volume":"1150","author":"King","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025111212071284900_CS-2025-7272C81","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.bbmt.2018.04.016","article-title":"Comprehensive analysis of the activation and proliferation kinetics and effector functions of human lymphocytes, and antigen presentation capacity of antigen-presenting cells in xenogeneic graft-versus-host disease","volume":"24","author":"Kawasaki","year":"2018","journal-title":"Biol. Blood Marrow Transplant"},{"key":"2025111212071284900_CS-2025-7272C82","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1497","article-title":"Graft-versus-leukaemia immunity is retained following treatment with post-transplant cyclophosphamide alone or combined with tocilizumab in humanised mice","volume":"13","author":"Sligar","year":"2024","journal-title":"Clin. Transl. Immunology"},{"key":"2025111212071284900_CS-2025-7272C83","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.4049\/jimmunol.0902458","article-title":"Endothelial cells augment the suppressive function of CD4+CD25+Foxp3+ regulatory T cells: involvement of programmed death-1 and IL-10","volume":"184","author":"Bedke","year":"2010","journal-title":"The Journal of Immunology"},{"key":"2025111212071284900_CS-2025-7272C84","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025111212071284900_CS-2025-7272C85","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1084\/jem.20090847","article-title":"PD-L1 regulates the development, maintenance, and function of induced regulatory T cells","volume":"206","author":"Francisco","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025111212071284900_CS-2025-7272C86","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0086551","article-title":"Role of lymphocyte activation gene-3 (lag-3) in conventional and regulatory T cell function in allogeneic transplantation","volume":"9","author":"Sega","year":"2014","journal-title":"PLoS ONE"},{"key":"2025111212071284900_CS-2025-7272C87","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1172\/JCI7894","article-title":"Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets","volume":"105","author":"Nikolic","year":"2000","journal-title":"J. Clin. Invest."},{"key":"2025111212071284900_CS-2025-7272C88","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bbmt.2018.10.007","article-title":"In vitro Th17-polarized human CD4+ T cells exacerbate xenogeneic graft-versus-host disease","volume":"25","author":"Delens","year":"2019","journal-title":"Biol. Blood Marrow Transplant"},{"key":"2025111212071284900_CS-2025-7272C89","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood-2008-06-162420","article-title":"In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations","volume":"113","author":"Carlson","year":"2009","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C90","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1016\/j.bbmt.2011.10.001","article-title":"The IL-17 differentiation pathway and its role in transplant outcome","volume":"18","author":"Serody","year":"2012","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025111212071284900_CS-2025-7272C91","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/00007890-199303000-00022","article-title":"The immunopathology of upper gastrointestinal acute graft-versus-host disease. Lymphoid cells and endothelial adhesion molecules","volume":"55","author":"Roy","year":"1993","journal-title":"Transplantation"},{"key":"2025111212071284900_CS-2025-7272C92","first-page":"648","article-title":"The pathogenesis of graft-versus-host reaction in the intrahepatic bile duct. An immunohistochemical study","volume":"39","author":"Tanaka","year":"1989","journal-title":"Acta Pathol. Jpn."},{"key":"2025111212071284900_CS-2025-7272C93","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.clml.2016.06.013","article-title":"Post-transplantation natural killer cell count: a predictor of acute graft-versus-host disease and survival outcomes after allogeneic hematopoietic stem cell transplantation","volume":"16","author":"Kim","year":"2016","journal-title":"Clin. Lymphoma. Myeloma Leuk"},{"key":"2025111212071284900_CS-2025-7272C94","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1365-2141.2007.06623.x","article-title":"Association of bone marrow natural killer cell dose with neutrophil recovery and chronic graft-versus-host disease after HLA identical sibling bone marrow transplants","volume":"138","author":"Larghero","year":"2007","journal-title":"Br. J. Haematol."},{"key":"2025111212071284900_CS-2025-7272C95","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.leukres.2011.11.009","article-title":"The impact of the dose of natural killer cells in the graft on severe acute graft-versus-host disease after unrelated bone marrow transplantation","volume":"36","author":"Tanaka","year":"2012","journal-title":"Leuk. Res."},{"key":"2025111212071284900_CS-2025-7272C96","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1182\/blood.2021013054","article-title":"Signatures of GVHD and relapse after posttransplant cyclophosphamide revealed by immune profiling and machine learning","volume":"139","author":"McCurdy","year":"2022","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C97","first-page":"2692","article-title":"Comparison of induction chemotherapy in NSG and NOD- Rag1 null IL2rg null mouse models of FLT3 mutant AML","volume":"130","author":"Mu","year":"2017","journal-title":"Blood"},{"key":"2025111212071284900_CS-2025-7272C98","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/s41409-024-02414-z","article-title":"Cardiac events occurring after allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide. Study conducted on behalf of the GETH-TC","volume":"59","author":"Salas","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"2025111212071284900_CS-2025-7272C99","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26135995","article-title":"Echocardiographic assessment of cardiac function in mouse models of heart disease","volume":"26","author":"Salerno","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"2025111212071284900_CS-2025-7272C100","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtcme.2025.06.001","article-title":"Osthole attenuates trastuzumab-induced cardiotoxicity in mice by enhancing autophagy via regulating the p38MAPK\/mTOR signaling pathway","author":"Hou","year":"2025","journal-title":"J. Tradit. Complement. Med."},{"key":"2025111212071284900_CS-2025-7272C101","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.01305","article-title":"Characterization and validation of a chronic model of cyclophosphamide-induced interstitial cystitis\/bladder pain syndrome in rats","volume":"11","author":"Aug\u00e9","year":"2020","journal-title":"Front. Pharmacol."},{"key":"2025111212071284900_CS-2025-7272C102","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.fct.2007.06.007","article-title":"A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters","volume":"45","author":"Ramaiah","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"2025111212071284900_CS-2025-7272C103","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2024.154020","article-title":"Preclinical liver toxicity models: advantages, limitations and recommendations","volume":"511","author":"Ezhilarasan","year":"2025","journal-title":"Toxicology"},{"key":"2025111212071284900_CS-2025-7272C104","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4103\/japtr.JAPTR_336_18","article-title":"Nephrotoxicity: role and significance of renal biomarkers in the early detection of acute renal injury","volume":"10","author":"Al-Naimi","year":"2019","journal-title":"J. Adv. Pharm. Technol. Res."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/139\/21\/1261\/979332\/cs-2025-7272.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/139\/21\/1261\/979332\/cs-2025-7272.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T17:07:28Z","timestamp":1762967248000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/139\/21\/1261\/236665\/Low-and-high-dose-post-transplant-cyclophosphamide"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":104,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11,12]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20257272","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,10,28]]}}}