{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:45:16Z","timestamp":1765547116975,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Ischemia\/reperfusion injury (IRI), acute rejection (AR), and delayed graft function (DGF) might occur as major complications following kidney transplantation. Thus, the identification of biomarkers for the IRI, AR, and\/or DGF development becomes crucial as it may help to guide post-transplant management. Natural killer (NK) cells, hepatic interstitial T-lymphocytes (T-Li), and NK-T cells are crucial in both innate and adaptive immunity after abdominal solid organ transplantation. Hence, the aim of this study was to evaluate the impact of the immune system after graft reperfusion during KT in adults in order to identify predictive biomarkers. Methods: The NK, T-Li, and NK-T phenotypes and concentrations were retrospectively analyzed in a consecutive series of liver perfusates obtained after organ procurement flushing the abdominal cavity recovered from deceased brain donors (DBDs). Their percentage was compared with the renal transplant recipients\u2019 characteristics with kidneys taken from the same DCDs. The hepatic perfusate cells were purified by density gradient centrifugation. Flow cytometric investigation was used to determine their phenotype with the following immunological markers in order to determine the relative percentage of T-Li, NK-T, and NK cells: CD3, CD4, CD8, and CD56. Results: 42 DBDs\u2019 liver perfusates were analyzed. The related clinical outcomes of kidney transplant recipients from 2010 to 2020 performed at our Institute were evaluated. Time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02) and the onset of secondary infection from a cytomegalovirus (p = 0.03) were significantly associated with the T-Li percentage. An increased relative risk (HR) of organ survival was significantly associated with the percent cell concentration of T-Li and time to DGF, on COX analysis, were (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). None relevant clinical outcomes in kidney transplant patients were associated with the specificity of the NK and NK-T cell proportions. Conclusions: A new potential role of T-Li cells was detected in the context of hepatic perfusate from DBDs. It could detect potential impacts in organ allocation, surgical procuring techniques, and in the analysis of IRI pathophysiological events.<\/jats:p>","DOI":"10.3390\/jcm12144786","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T04:27:13Z","timestamp":1689827233000},"page":"4786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of T Lymphocytes Isolated from Liver Perfusate of Deceased Brain Donors on Kidney Transplantation: Preliminary Evidence and Future Directions"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3987-9262","authenticated-orcid":false,"given":"Duilio","family":"Pagano","sequence":"first","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-6270","authenticated-orcid":false,"given":"Ester","family":"Badami","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy"},{"name":"Ri.MED Foundation, 90133 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0482-6729","authenticated-orcid":false,"given":"Giovanni","family":"Zito","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-8005","authenticated-orcid":false,"given":"Pier Giulio","family":"Conaldi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4946-512X","authenticated-orcid":false,"given":"Ivan","family":"Vella","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Buscemi","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-9861","authenticated-orcid":false,"given":"Giandomenico","family":"Amico","sequence":"additional","affiliation":[{"name":"Ri.MED Foundation, 90133 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalia","family":"Bus\u00e0","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Salis","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Li Petri","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"di Francesco","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Calamia","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Bonsignore","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Tropea","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Accardo","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Piazza","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-8035","authenticated-orcid":false,"given":"Salvatore","family":"Gruttadauria","sequence":"additional","affiliation":[{"name":"Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy"},{"name":"Department of Surgery and Surgical and Medical Specialties, University of Catania, 95124 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MOT.0000000000001034","article-title":"Delayed graft function: Current status and future directions","volume":"28","author":"Swanson","year":"2023","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1097\/TP.0000000000002275","article-title":"Association Between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome After Deceased Donor Kidney Transplantation","volume":"103","author":"Lim","year":"2019","journal-title":"Transplantation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1172\/JCI133595","article-title":"Phase I trial of donor-derived modified immune cell infusion in kidney transplantation","volume":"130","author":"Morath","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.1038\/s41598-019-42401-9","article-title":"Characterization of donor and recipient CD8+ tissue-resident memory T cells in transplant nephrectomies","volume":"9","author":"Dieterich","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jahn, N., Sack, U., Stehr, S., V\u00f6elker, M.T., Laudi, S., Seehofer, D., Atay, S., Zgoura, P., Viebahn, R., and Boldt, A. (2022). The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney Transplantation. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206148"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.immuni.2018.12.011","article-title":"Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity","volume":"50","author":"Jayachandran","year":"2019","journal-title":"Immunity"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zito, G., Miceli, V., Carcione, C., Bus\u00e0, R., Bulati, M., Gallo, A., Iannolo, G., Pagano, D., and Conaldi, P.G. (2022). Human Amnion-Derived Mesenchymal Stromal\/Stem Cells Pre-Conditioning Inhibits Inflammation and Apoptosis of Immune and Parenchymal Cells in an In Vitro Model of Liver Ischemia\/Reperfusion. Cells, 11.","DOI":"10.3390\/cells11040709"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/ki.2010.416","article-title":"T-cell alloimmunity and chronic allograft dysfunction","volume":"78","author":"Safinia","year":"2010","journal-title":"Kidney Int. Suppl."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1056\/NEJMoa074191","article-title":"Tolerance and chimerism after renal and hematopoietic-cell transplantation","volume":"358","author":"Scandling","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1046\/j.1523-1755.1999.00631.x","article-title":"Peripheral donor leukocytes prolong survival of rat renal allografts","volume":"56","author":"Noris","year":"1999","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/jlb.66.2.310","article-title":"Infusion of donor leukocytes to induce tolerance in organ allograft recipients","volume":"66","author":"Salgar","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"ref_12","first-page":"136","article-title":"Donor-specific T-cell reactivity identifies kidney transplant patients in whom immunosuppressive therapy can be safely reduced","volume":"70","author":"Vaessen","year":"2000","journal-title":"Transplantation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/TP.0000000000002322","article-title":"Liver Perfusate Natural Killer Cells from Deceased Brain Donors and Association with Acute Cellular Rejection after Liver Transplantation: A Time-to-Rejection Analysis","volume":"103","author":"Pagano","year":"2019","journal-title":"Transplantation"},{"key":"ref_14","unstructured":"Badami, E. (2019). NK-Mediated Immunotherapy and Uses Thereof. (20190322985), U.S. Patent."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Carreca, A.P., Gaetani, M., Bus\u00e0, R., Francipane, M.G., Gulotta, M.R., Perricone, U., Iannolo, G., Russelli, G., Carcione, C., and Conaldi, P.G. (2022). Galectin-9 and Interferon-Gamma Are Released by Natural Killer Cells upon Activation with Interferon-Alpha and Orchestrate the Suppression of Hepatitis C Virus Infection. Viruses, 14.","DOI":"10.3390\/v14071538"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1016\/j.transproceed.2019.02.075","article-title":"Crucial Role of Extended Criteria Donors in Deceased Donor Single Kidney Transplantation to Face Chronic Shortage in the Heart of the Mediterranean Basin: A Single-Center Experience","volume":"51","author":"Bonsignore","year":"2019","journal-title":"Transplant. Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.dld.2013.11.004","article-title":"A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study","volume":"46","author":"Angelico","year":"2014","journal-title":"Dig. Liver Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.amjsurg.2021.06.019","article-title":"Machine perfusion of kidney allografts affects early but not late graft function","volume":"223","author":"Singh","year":"2022","journal-title":"Am. J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.kint.2022.12.025","article-title":"Kidney-specific metabolomic profiling in machine perfusate","volume":"103","author":"Rhee","year":"2023","journal-title":"Kidney Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11100","DOI":"10.3389\/ti.2023.11100","article-title":"Organ Reconditioning and Machine Perfusion in Transplantation","volume":"36","author":"Bellini","year":"2023","journal-title":"Transpl. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1056\/NEJMoa2118265","article-title":"Hypothermia or Machine Perfusion in Kidney Donors","volume":"388","author":"Malinoski","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jhep.2022.12.030","article-title":"A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation","volume":"78","author":"Schlegel","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1097\/TP.0000000000004098","article-title":"Normothermic Ex Vivo Kidney Perfusion for Human Kidney Transplantation: First North American Results","volume":"106","author":"Mazilescu","year":"2022","journal-title":"Transplantation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10749","DOI":"10.3389\/ti.2023.10749","article-title":"Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients","volume":"36","author":"Mawad","year":"2023","journal-title":"Transpl. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.kint.2022.11.020","article-title":"Untargeted metabolomics of perfusate and their association with hypothermic machine perfusion and allograft failure","volume":"103","author":"Liu","year":"2023","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1177\/0267659120938928","article-title":"Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death","volume":"36","author":"Peris","year":"2021","journal-title":"Perfusion"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101819","DOI":"10.1016\/j.eclinm.2022.101819","article-title":"Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): A randomised controlled trial","volume":"56","author":"Stringer","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e052845","DOI":"10.1136\/bmjopen-2021-052845","article-title":"Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: Study protocol for a multicentre randomised controlled trial (HYPOREME)","volume":"12","author":"Canet","year":"2022","journal-title":"BMJ Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e066128","DOI":"10.1136\/bmjopen-2022-066128","article-title":"Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): Protocol for a multicentre, open-label, phase II, randomised controlled trial","volume":"12","author":"Morath","year":"2022","journal-title":"BMJ Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.3748\/wjg.15.2074","article-title":"Clinical applications of hepatocyte transplantation","volume":"15","author":"Pietrosi","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.3748\/wjg.15.4556","article-title":"Early graft dysfunction following adult-to-adult living-related liver transplantation: Predictive factors and outcomes","volume":"15","author":"Gruttadauria","year":"2009","journal-title":"World J. Gastroenterol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/14\/4786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:15:21Z","timestamp":1760127321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/14\/4786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,20]]},"references-count":31,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jcm12144786"],"URL":"https:\/\/doi.org\/10.3390\/jcm12144786","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2023,7,20]]}}}