{"doi":"10.1371/journal.ppat.1008885","title":"CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis","abstract":"Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded.","journal":"PLoS Pathogens","year":2020,"id":97345,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333570,"name":"Bonnie Chen","orcid":"0000-0002-7360-0379","position":1,"is_corresponding":false},{"id":415761,"name":"Mike Fang","orcid":"0000-0002-8318-1016","position":2,"is_corresponding":false},{"id":481417,"name":"Daria M. Potashnikova","orcid":"0000-0002-0098-827X","position":3,"is_corresponding":false},{"id":481418,"name":"Alexey A. Komissarov","orcid":"0000-0003-1018-5195","position":4,"is_corresponding":false},{"id":481419,"name":"Аnna Lebedeva","orcid":"0000-0001-5274-7200","position":5,"is_corresponding":false},{"id":481420,"name":"Gillian M Michaelson","orcid":"0000-0003-1499-7721","position":6,"is_corresponding":false},{"id":482158,"name":"Jonathan M. Wyrick","orcid":null,"position":7,"is_corresponding":false},{"id":333569,"name":"Stephen R. Morris","orcid":"0000-0003-3232-8329","position":8,"is_corresponding":false},{"id":333573,"name":"Scott F. Sieg","orcid":"0000-0002-1769-8682","position":9,"is_corresponding":false},{"id":244985,"name":"Mirko Paiardini","orcid":"0000-0002-7276-3600","position":10,"is_corresponding":false},{"id":258352,"name":"François Villinger","orcid":"0000-0002-7790-2008","position":11,"is_corresponding":false},{"id":481421,"name":"Karem C. Harth","orcid":"0000-0001-5241-4916","position":12,"is_corresponding":false},{"id":398214,"name":"Vikram S. Kashyap","orcid":"0000-0003-1780-979X","position":13,"is_corresponding":false},{"id":105516,"name":"Mark J. Cameron","orcid":"0000-0003-4768-4094","position":14,"is_corresponding":false},{"id":105517,"name":"Cheryl Cameron","orcid":"0000-0002-0574-3781","position":15,"is_corresponding":false},{"id":481422,"name":"Elena Vasilieva","orcid":"0000-0003-4111-0874","position":16,"is_corresponding":false},{"id":344429,"name":"Leonid Margolis","orcid":"0000-0002-1960-1928","position":17,"is_corresponding":false},{"id":333575,"name":"Souheil‐Antoine Younes","orcid":"0000-0003-2186-7140","position":18,"is_corresponding":false},{"id":295813,"name":"Nicholas Funderburg","orcid":"0000-0003-3113-1217","position":19,"is_corresponding":false},{"id":333574,"name":"David A. Zidar","orcid":"0000-0002-2805-3986","position":20,"is_corresponding":false},{"id":262177,"name":"Michael M. Lederman","orcid":"0000-0001-9247-8025","position":21,"is_corresponding":false},{"id":333577,"name":"Michael L. Freeman","orcid":"0000-0002-7690-5258","position":22,"is_corresponding":false},{"id":333571,"name":"Soumya Panigrahi","orcid":"0000-0002-5024-9459","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T22:35:34.520494Z","pmid":"32976527","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":[]}