{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T09:28:19Z","timestamp":1778405299302,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Responses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with an abnormal biopsy, the majority of CD8<jats:sup>+<\/jats:sup> DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8<jats:sup>+<\/jats:sup> DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1516772","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T12:20:46Z","timestamp":1738844446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection"],"prefix":"10.3389","volume":"16","author":[{"given":"Jes 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