{"doi":"10.1016/j.ymthe.2026.01.024","title":"CD8+ T cell differentiation into NK-like effector cells drives transplant rejection","abstract":null,"journal":"Molecular Therapy","year":2026,"id":608333,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":758483,"name":"Stephanie G. Yi","orcid":"0000-0003-4365-578X","position":1,"is_corresponding":false},{"id":329071,"name":"Yulin Dai","orcid":"0000-0003-1874-7893","position":2,"is_corresponding":false},{"id":1562327,"name":"Luan Truong","orcid":null,"position":3,"is_corresponding":false},{"id":1562328,"name":"Lillian W. Gaber","orcid":null,"position":4,"is_corresponding":false},{"id":1562329,"name":"Richard J. Knight","orcid":null,"position":5,"is_corresponding":false},{"id":329073,"name":"Xiang Xiao","orcid":"0000-0001-6644-6118","position":6,"is_corresponding":false},{"id":720153,"name":"Rafik M. Ghobrial","orcid":null,"position":7,"is_corresponding":false},{"id":1562330,"name":"Xian C. Li","orcid":null,"position":8,"is_corresponding":false},{"id":13182,"name":"Zhongming Zhao","orcid":"0000-0002-3477-0914","position":9,"is_corresponding":false},{"id":329075,"name":"Wenhao Chen","orcid":"0000-0002-0626-3739","position":10,"is_corresponding":false},{"id":758484,"name":"A. Osama Gaber","orcid":"0000-0002-0743-4974","position":11,"is_corresponding":false},{"id":329070,"name":"Dawei Zou","orcid":"0000-0003-4130-0280","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CD8+ T cell differentiation into NK-like effector cells drives transplant rejection","abstract":"T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8 + T cell subset exhibiting killer cell lectin-like receptor (KLR) + NK-like features. Mechanistic studies in mice showed that the KLR + subset emerged de novo post-transplantation and dominated the CD8 + T cell infiltrate in rejecting allografts. These NK-like CD8 + T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the generation of NK-like CD8 + T cells; however, the persistence of these cells ultimately led to rejection. Notably, combining costimulation blockade with mTOR inhibition completely abrogated their generation and enabled transplant acceptance. Together, these findings identify KLR + NK-like CD8 + T cells as key mediators of transplant rejection, highlighting the need for more effective strategies to block their differentiation and improve transplant outcomes.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41572631","pmcid":null,"openalex_id":"https://openalex.org/W7125159915","authors":[],"funders":[{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"2R56AI132492","title":null},{"funder_name":"National Library of Medicine","grant_id":"R01LM012806","title":null},{"funder_name":"American Society of Transplantation","grant_id":"1451902","title":null},{"funder_name":"Cancer Prevention and Research Institute of Texas","grant_id":"RP240610","title":null}],"total_grants":4,"fwci":4.1573,"citation_percentile":0.87836402,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.ymthe.2026.01.024","host_type":"journal"},{"url":"https://doi.org/10.1016/j.ymthe.2026.01.024","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1525001626000250?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1525001626000250?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41572631","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12967240/","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","Renal Transplantation Outcomes and Treatments"],"mesh_terms":["Interferon Regulatory Factor-4","Animals","Cell Differentiation","Graft Rejection","Humans","Killer Cells, Natural","Biomarkers","Kidney Transplantation","CD8-Positive T-Lymphocytes","Gene Expression Profiling","Interferon Regulatory Factors","Mice","TOR Serine-Threonine Kinases"],"keywords":["Blockade","Effector","PI3K/AKT/mTOR pathway","Transplantation","Transplant rejection","Cytotoxic T cell","Transcriptome","T cell","CD8"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T11:57:07.112861Z","pmid":null,"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":[]}