{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T08:33:14Z","timestamp":1793435594240,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100032559","name":"Breakthrough T1D","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Islet xenotransplantation is a strategy for treatment of Type 1 Diabetes, but immune\u2010mediated rejection limits graft survival. This study investigated a strategy with flow cytometry\u2013based immune monitoring to evaluate immunosuppressive therapy and provide indicators of graft rejection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Porcine neonatal islet cell clusters (NICC) from GTKO\u2010hCD55\u2010hCD59 transgenic pigs were transplanted into streptozotocin\u2010induced diabetic baboons (\n                      <jats:italic>n =<\/jats:italic>\n                      10). Recipients received anti\u2010CD2 induction with anti\u2010CD154, Belatacept, and full\u2010dose (\n                      <jats:italic>n =<\/jats:italic>\n                      7) or reduced\/no dose Tacrolimus (\n                      <jats:italic>n =<\/jats:italic>\n                      3). Leukocyte subsets and activation status were monitored using multiplex flow cytometry. Graft function was assessed by blood glucose measurements, porcine C\u2010peptide ELISA, and histological analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Porcine C\u2010peptide was detected in all recipients. Seven animals receiving full\u2010dose Tacrolimus maintained NICC function for up to 675 days, whereas three experienced acute rejection within two months. Flow cytometry generated absolute leukocyte counts equivalent to standard full blood counts (Deming regression slope 0.91\u20131.03, p&lt;0.001), while requiring less blood (50\u00a0\u00b5l vs \u223c500\u00a0\u00b5l) and processing time (50\u00b115\u00a0vs 150\u00b130\u00a0min). Anti\u2010CD2 treatment significantly reduced unoccupied surface CD2 on circulating T cells (mean 73.21%, range 55.26\u201391.16%, p&lt;0.001). Long\u2010term graft survival was associated with greater first\u2010month T\u2010cell suppression (36.47%, 13.35\u201350.75%) than acute rejection (176.28%, 171.26\u2013181.31%). Following immunosuppression withdrawal, lymphocyte counts increased by 40%\u2013142% in all recipients. Multiplex immunofluorescence of endpoint grafts from these IS\u2010free animals revealed cell\u2010mediated destruction with increased lymphocyte infiltration and activated cytotoxic CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Multiplex flow cytometry provides a reliable method for immune monitoring in islet xenotransplantation and may help predict graft rejection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70170","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:50:33Z","timestamp":1790211033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Flow Cytometric Immune Profiling Enables Early Detection of Rejection in Islet Xenotransplantation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6579-1104","authenticated-orcid":false,"given":"Huu Thanh","family":"Le","sequence":"first","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1828-4644","authenticated-orcid":false,"given":"Erin","family":"Fuller","sequence":"additional","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauen","family":"Joo","sequence":"additional","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-0743","authenticated-orcid":false,"given":"Evelyn J.","family":"Salvaris","sequence":"additional","affiliation":[{"name":"Immunology Research Centre St. Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adwin","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-8654","authenticated-orcid":false,"given":"Yivee","family":"Chew","sequence":"additional","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hu","sequence":"additional","affiliation":[{"name":"Translational Transplantation Therapies Westmead Institute for Medical Research  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-4952","authenticated-orcid":false,"given":"Francesco","family":"Ierino","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-5542","authenticated-orcid":false,"given":"Mark B.","family":"Nottle","sequence":"additional","affiliation":[{"name":"School of Biomedicine, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia 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