{"doi":"10.1101/2025.08.06.668764","title":"Angiogenic CD8 T cells from PWH induce Granzymes-dependent PAR1 activation promoting endothelial inflammation","abstract":"Abstract In people with HIV (PWH), T cell immune activation and endothelial inflammation are contributors of the increased cardiovascular risk, however the mechanisms remain poorly understood. PAR1 connects the coagulation cascade, endothelial cells and CD8 T cells at the site of endothelial inflammation and we hypothesized that HIV driven CD8 T cell immune activation alters endothelial repair mechanisms. Endothelial repair is partially mediated by angiogenic T (T ang ) cells that facilitate proliferation of endothelial cells, and differentiation of endothelial progenitor cells at site of vascular injury. During LCMV infection, we identified a subset of CD31 high CD8 T cells that exhibited a long-lived memory precursor phenotype (CD127 + KLRG1 - ) and secreted the proangiogenic cytokine vascular endothelial growth factor (VEGF) after viral control. Furthermore, in PWH, the frequencies of CD8 T ang cells were reduced and showed an activated phenotype and expression of granzymes. GZMA + GZMB + CD8 T ang cells correlated with atherosclerotic cardiovascular disease (ASCVD) risk. In vitro , granzyme dependent PAR1 activation led to calcium mobilization and secretion of proinflammatory cytokines IL-6, IL-8 and angiopoietin-2 by primary human endothelial cells. Altogether, these findings suggest that CD8 T cells are involved in immunity against viruses and endothelial homeostasis and HIV driven immune activation alters these functions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572241,"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":0.9596,"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":1359294,"name":"Chinmayee Mehta","orcid":null,"position":1,"is_corresponding":false},{"id":1235445,"name":"Cooper James","orcid":null,"position":2,"is_corresponding":false},{"id":793044,"name":"Jinya Chen","orcid":"0000-0002-2519-5356","position":3,"is_corresponding":false},{"id":361651,"name":"Hui Chen","orcid":"0000-0001-5704-5486","position":4,"is_corresponding":false},{"id":313531,"name":"Gerard P. Ahern","orcid":"0000-0001-5317-7262","position":5,"is_corresponding":false},{"id":484320,"name":"Ziang Zhu","orcid":"0009-0008-4231-7213","position":6,"is_corresponding":false},{"id":1478880,"name":"Maitane Faus Cid","orcid":null,"position":7,"is_corresponding":false},{"id":967167,"name":"Maryam Abdussamad","orcid":null,"position":8,"is_corresponding":false},{"id":1478881,"name":"Shiwen Yu","orcid":null,"position":9,"is_corresponding":false},{"id":720329,"name":"Jai Kumar","orcid":"0000-0002-3340-1324","position":10,"is_corresponding":false},{"id":444050,"name":"Princy Kumar","orcid":"0000-0002-5994-2727","position":11,"is_corresponding":false},{"id":270868,"name":"Colleen Hadigan","orcid":"0000-0003-0642-7817","position":12,"is_corresponding":false},{"id":1478882,"name":"Kyle A. DiVito","orcid":null,"position":13,"is_corresponding":false},{"id":235863,"name":"Dorian B. McGavern","orcid":"0000-0001-9568-545X","position":14,"is_corresponding":false},{"id":295928,"name":"Leonid A. Pobezinsky","orcid":"0000-0002-6115-3559","position":15,"is_corresponding":false},{"id":474439,"name":"Marta Catálfamo","orcid":null,"position":16,"is_corresponding":false},{"id":793043,"name":"Tong Li","orcid":"0000-0002-4283-0091","position":0,"is_corresponding":true}],"reference_count":142,"raw_metadata":null,"created_at":"2026-07-19T02:57:23.653298Z","pmid":"41031030","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":[]}