{"doi":"10.1093/infdis/jiab204","title":"Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints","abstract":"BACKGROUND: PD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV. METHODS: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses. RESULTS: PD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3- in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted. CONCLUSIONS: Children with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1-directed immunotherapies for pediatric HIV remission and cure.","journal":"The Journal of Infectious Diseases","year":2021,"id":209381,"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":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":796991,"name":"Julia Foldi","orcid":"0000-0002-7504-867X","position":1,"is_corresponding":false},{"id":796992,"name":"Matthew Generoso","orcid":"0000-0002-8568-8638","position":2,"is_corresponding":false},{"id":797552,"name":"Bret McCarty","orcid":null,"position":3,"is_corresponding":false},{"id":797553,"name":"Aparna Alankar","orcid":null,"position":4,"is_corresponding":false},{"id":797554,"name":"Max Kilberg","orcid":null,"position":5,"is_corresponding":false},{"id":797555,"name":"Mussa Mwamzuka","orcid":null,"position":6,"is_corresponding":false},{"id":797556,"name":"Fatma Marshed","orcid":null,"position":7,"is_corresponding":false},{"id":797557,"name":"Aabid Ahmed","orcid":null,"position":8,"is_corresponding":false},{"id":329106,"name":"Mengling Liu","orcid":"0000-0001-9758-8522","position":9,"is_corresponding":false},{"id":444710,"name":"William Borkowsky","orcid":null,"position":10,"is_corresponding":false},{"id":235097,"name":"Derya Unutmaz","orcid":"0000-0001-8898-6633","position":11,"is_corresponding":false},{"id":333679,"name":"Alka Khaitan","orcid":"0000-0002-7316-4300","position":12,"is_corresponding":false},{"id":796990,"name":"Janki Tailor","orcid":"0000-0001-9243-7004","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:52:05.171356Z","pmid":"33864071","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":[]}