{"doi":"10.3389/fimmu.2025.1516772","title":"Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection","abstract":"Introduction 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. Methods DRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4 + and CD8 + 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. Results In patients with an abnormal biopsy, the majority of CD8 + DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8 + 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. Discussion 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.","journal":"Frontiers in Immunology","year":2025,"id":538720,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9393,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":218604,"name":"Barbara L. Banbury","orcid":"0000-0001-7332-7117","position":1,"is_corresponding":false},{"id":1425980,"name":"Erika L. Schumacher","orcid":null,"position":2,"is_corresponding":false},{"id":1425597,"name":"Jie He","orcid":"0000-0001-6961-8421","position":3,"is_corresponding":false},{"id":1425598,"name":"Yuvaraj Sambandam","orcid":"0000-0002-5855-7085","position":4,"is_corresponding":false},{"id":460601,"name":"Paul Fields","orcid":"0000-0002-9608-6464","position":5,"is_corresponding":false},{"id":301629,"name":"Lorenzo Gallon","orcid":"0000-0002-6094-1027","position":6,"is_corresponding":false},{"id":1425599,"name":"James M. Mathew","orcid":"0000-0002-5667-750X","position":7,"is_corresponding":false},{"id":302545,"name":"Joseph R. Leventhal","orcid":"0000-0003-1604-9207","position":8,"is_corresponding":false},{"id":1237518,"name":"Jes M. Sanders","orcid":"0000-0001-7465-2480","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:52:25.799399Z","pmid":"39981250","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}