{"doi":"10.1016/j.ajt.2025.10.015","title":"Proinflammatory and cytotoxic CD38+HLA-DR+ effector memory CD8+ T cells are peripherally expanded in human cardiac allograft vasculopathy","abstract":"Interferon-γ (IFNG) is thought to play a central role in the pathogenesis of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) patients. However, peripheral lymphocytes participating in the IFNG-axis remain largely unknown in human CAV. Using peripheral blood mononuclear cells (PBMC) from International Society for Heart and Lung Transplant (ISHLT) grade 2 or 3 CAV (high-grade CAV) and normal HTx patients, we performed high dimensional analysis (high-grade CAV, n=6; normal HTx, n=12) with cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and VDJ sequencing (VDJ-seq) and validated the findings by flow cytometry in an independent cohort (high-grade CAV, n=11; normal HTx, n=12). Among the major immune cell populations, CD8 + T cells expressed IFNG most highly. Among the CD8 + T cell clusters, the CD38 + HLA-DR + CD8 + effector memory T (Tem) cell cluster was significantly increased in CAV compared to normal HTx PBMC samples. This cluster showed clonal expansion, increased IFNG signaling, and enhanced cytotoxicity with granzyme B (GZMB) and perforin 1 (PRF1) overexpression. CD38 + HLA-DR + CD8 + T cells also infiltrated the intima of explanted CAV coronary arteries. Thus, we conclude that circulating CD38 + HLA-DR + CD8 + Tem cells may contribute to the pathogenic IFNG-axis in human CAV.","journal":"American Journal of Transplantation","year":2025,"id":579047,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":866044,"name":"Sujit Silas Armstrong Suthahar","orcid":"0000-0002-2538-4691","position":1,"is_corresponding":false},{"id":490438,"name":"Payel Roy","orcid":"0000-0003-2511-068X","position":2,"is_corresponding":false},{"id":585616,"name":"Vasantika Suryawanshi","orcid":"0000-0003-1497-7480","position":3,"is_corresponding":false},{"id":272882,"name":"Runpei Wu","orcid":null,"position":4,"is_corresponding":false},{"id":912964,"name":"Erpei Wang","orcid":null,"position":5,"is_corresponding":false},{"id":878440,"name":"Felix Sebastian Nettersheim","orcid":"0000-0002-4090-3357","position":6,"is_corresponding":false},{"id":1391786,"name":"A. Bellapu","orcid":"0000-0003-0605-1063","position":7,"is_corresponding":false},{"id":729849,"name":"Katarzyna Dobaczewska","orcid":"0000-0002-6377-018X","position":8,"is_corresponding":false},{"id":104943,"name":"Cheryl Kim","orcid":"0000-0001-9535-5709","position":9,"is_corresponding":false},{"id":423680,"name":"Florin Vaida","orcid":"0000-0002-2256-4611","position":10,"is_corresponding":false},{"id":368450,"name":"Gerald P. Morris","orcid":"0000-0002-1097-4453","position":11,"is_corresponding":false},{"id":324398,"name":"Klaus Ley","orcid":"0000-0001-9339-3672","position":12,"is_corresponding":false},{"id":854965,"name":"Paul Kim","orcid":"0000-0002-1755-6182","position":13,"is_corresponding":false},{"id":271800,"name":"Yuko Tada","orcid":"0000-0003-1410-9894","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:58:24.957414Z","pmid":"41138970","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":[]}