{"doi":"10.1016/j.celrep.2025.116181","title":"Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles","abstract":"B cell follicles (BCFs) in the lymph node are a major sanctuary for HIV reservoirs. Immune regulatory mechanisms hindering cytolytic CD8 + responses at these sites are poorly characterized, likely enabling HIV persistence. Spatial transcriptomics and high-dimensional histocytometry were used to define CD8 + T cell function and immune regulation in lymph node (LN) follicles of people living with HIV (PLWH), at various stages of antiretroviral therapy (ART) treatment. Histocytometry demonstrated that CD8 + T cells infiltrating BCFs mostly lacked granzyme B expression, coinciding with reduced chromatin access at cytolytic gene loci in dissociated lymph node cells. Spatial transcriptomics confirmed the immune regulatory microenvironment of HIV-infected BCFs, particularly exhibiting upregulation of HLA-E. Additional fluorescence-activated cell sorting (FACS) analysis identified a subset of LN CD8 + T cells expressing the NKG2A-interacting partner of HLA-E, with reduced granzyme B expression. These findings suggest that regulation of follicular CD8 + T cells at the HLA-E-NKG2A axis may be a key mechanism for HIV immune evasion.","journal":"Cell Reports","year":2025,"id":514488,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":689781,"name":"Leonard Mvaya","orcid":"0000-0002-5376-1706","position":1,"is_corresponding":false},{"id":831807,"name":"Trevor Khaba","orcid":null,"position":2,"is_corresponding":false},{"id":933504,"name":"Namani Ngema","orcid":null,"position":3,"is_corresponding":false},{"id":933132,"name":"Werner Smidt","orcid":"0000-0002-6197-4103","position":4,"is_corresponding":false},{"id":1377712,"name":"Sibongiseni Msipa","orcid":null,"position":5,"is_corresponding":false},{"id":933502,"name":"Bongiwe Mahlobo","orcid":null,"position":6,"is_corresponding":false},{"id":831809,"name":"Thandekile Ngubane","orcid":null,"position":7,"is_corresponding":false},{"id":252000,"name":"Krista L. Dong","orcid":"0000-0002-2038-3518","position":8,"is_corresponding":false},{"id":831810,"name":"Ismail Jajbhay","orcid":null,"position":9,"is_corresponding":false},{"id":831811,"name":"Johan Pansegrouw","orcid":null,"position":10,"is_corresponding":false},{"id":324159,"name":"Kondwani Jambo","orcid":"0000-0002-3195-2210","position":11,"is_corresponding":false},{"id":252001,"name":"Zaza M. Ndhlovu","orcid":"0000-0002-2708-3315","position":12,"is_corresponding":false},{"id":776041,"name":"Andrea Olga Papadopoulos","orcid":"0000-0001-5317-1418","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:48:29.165853Z","pmid":"40849901","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":[]}