{"doi":"10.1101/2022.01.11.475845","title":"Inflammatory CD4/CD8 double positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology","abstract":"Abstract An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-vs-host disease (GVHD) while preserving the graft-vs-leukemia (GVL) activity of donor T cells. From an observational clinical study of adult allo-HCT recipients, we identified a CD4+/CD8+ double positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of ≥ grade 2 GVHD. Using an established xenogeneic transplant model, we reveal that the DPT population develop from antigen stimulated CD8 T cells which become transcriptionally, metabolically and phenotypically distinct from single-positive CD4 and CD8 T cells. Isolated DPTs were sufficient to mediate xeno-GVHD pathology when re-transplanted into naive mice but provided no survival benefit when mice were challenged with a human B-ALL cell line. Overall, this study reveals human DPTs as a T cell population directly involved with GVHD pathology. One Sentence Summary Human CD4+/CD8+ double positive T cells (DPTs) mediate xenogeneic GVHD but possess limited GVL activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299735,"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":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":990047,"name":"David P Turicek","orcid":"0000-0003-0837-2688","position":1,"is_corresponding":false},{"id":990048,"name":"Jeremiah Riendeau","orcid":"0000-0002-3014-2849","position":2,"is_corresponding":false},{"id":275525,"name":"Sean J. McIlwain","orcid":"0000-0002-3820-8400","position":3,"is_corresponding":false},{"id":451648,"name":"Emmanuel Contreras Guzman","orcid":"0000-0002-1929-3961","position":4,"is_corresponding":false},{"id":990049,"name":"Kalyan Nadiminti","orcid":"0000-0001-9625-1178","position":5,"is_corresponding":false},{"id":338813,"name":"Amy W. Hudson","orcid":"0000-0001-9718-6910","position":6,"is_corresponding":false},{"id":268267,"name":"Natalie S. Callander","orcid":"0000-0002-6975-1086","position":7,"is_corresponding":false},{"id":108082,"name":"Melissa C. Skala","orcid":"0000-0002-6320-7637","position":8,"is_corresponding":false},{"id":338814,"name":"Jenny E. Gumperz","orcid":"0000-0003-1852-2192","position":9,"is_corresponding":false},{"id":277447,"name":"Peiman Hematti","orcid":"0000-0001-5836-4497","position":10,"is_corresponding":false},{"id":277448,"name":"Christian M. Capitini","orcid":"0000-0002-2276-6731","position":11,"is_corresponding":false},{"id":338812,"name":"Nicholas J Hess","orcid":"0000-0001-5720-9305","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","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":[]}