{"doi":"10.1172/jci169309","title":"Anti–PD-1 chimeric antigen receptor T cells efficiently target SIV-infected CD4+ T cells in germinal centers","abstract":"Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8+ memory T cells. These data indicate anti-PD-1 CAR T cells depleted PD-1+ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.","journal":"Journal of Clinical Investigation","year":2024,"id":424559,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":684889,"name":"Yoshinori Fukazawa","orcid":"0000-0001-6613-5029","position":1,"is_corresponding":false},{"id":345517,"name":"Christopher W. Peterson","orcid":"0000-0002-3215-8924","position":2,"is_corresponding":false},{"id":766913,"name":"Françoise Haeseleer","orcid":"0000-0003-1887-1798","position":3,"is_corresponding":false},{"id":1222161,"name":"Manuel Medina","orcid":null,"position":4,"is_corresponding":false},{"id":1222162,"name":"Shelby Hoffmeister","orcid":null,"position":5,"is_corresponding":false},{"id":1222163,"name":"Derick M. Duell","orcid":null,"position":6,"is_corresponding":false},{"id":685750,"name":"Benjamin Varco-Merth","orcid":null,"position":7,"is_corresponding":false},{"id":475214,"name":"Sandra Dross","orcid":"0000-0003-1013-6828","position":8,"is_corresponding":false},{"id":552323,"name":"Haesun Park","orcid":"0000-0001-6259-7170","position":9,"is_corresponding":false},{"id":525542,"name":"Caralyn S. Labriola","orcid":"0000-0002-8271-6242","position":10,"is_corresponding":false},{"id":263668,"name":"Michael K. Axthelm","orcid":"0000-0002-1984-5906","position":11,"is_corresponding":false},{"id":534222,"name":"Robert D. Murnane","orcid":null,"position":12,"is_corresponding":false},{"id":344045,"name":"Jeremy Smedley","orcid":"0000-0003-3369-4662","position":13,"is_corresponding":false},{"id":672219,"name":"Lei Jin","orcid":"0000-0002-7841-7266","position":14,"is_corresponding":false},{"id":901851,"name":"Jiaxin Gong","orcid":"0000-0001-5101-3109","position":15,"is_corresponding":false},{"id":345513,"name":"Blake J. Rust","orcid":"0000-0002-7197-0990","position":16,"is_corresponding":false},{"id":225390,"name":"Deborah H. Fuller","orcid":"0000-0001-7315-2441","position":17,"is_corresponding":false},{"id":104354,"name":"Hans‐Peter Kiem","orcid":"0000-0001-5949-4947","position":18,"is_corresponding":false},{"id":246463,"name":"Louis J. Picker","orcid":"0000-0003-0546-398X","position":19,"is_corresponding":false},{"id":277149,"name":"Afam A. Okoye","orcid":"0000-0001-9671-550X","position":20,"is_corresponding":false},{"id":96348,"name":"Lawrence Corey","orcid":"0000-0002-2179-2436","position":21,"is_corresponding":false},{"id":766915,"name":"Karsten Eichholz","orcid":"0000-0001-8362-1563","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"38557496","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":[]}