{"doi":"10.1007/s13365-024-01223-w","title":"Dynamics of peripheral T cell exhaustion and monocyte subpopulations in neurocognitive impairment and brain atrophy in chronic HIV infection","abstract":"Abstract Background HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood. Methods We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models. Results Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1 + and/or TIM-3 + were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers. Conclusions This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16 + monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.","journal":"Journal of NeuroVirology","year":2024,"id":448861,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":1268229,"name":"Isabelle E. Yazel Eiser","orcid":null,"position":1,"is_corresponding":false},{"id":754714,"name":"Kalpana J. Kallianpur","orcid":"0000-0002-9978-097X","position":2,"is_corresponding":false},{"id":1268230,"name":"Louie Mar Gangcuangco","orcid":null,"position":3,"is_corresponding":false},{"id":657102,"name":"Dominic C. Chow","orcid":"0000-0001-7395-038X","position":4,"is_corresponding":false},{"id":69472,"name":"Lishomwa C. Ndhlovu","orcid":"0000-0001-5427-4187","position":5,"is_corresponding":false},{"id":225568,"name":"Robert Paul","orcid":"0000-0003-4225-6103","position":6,"is_corresponding":false},{"id":535328,"name":"Cecilia M. Shikuma","orcid":"0000-0003-0114-1262","position":7,"is_corresponding":false},{"id":535940,"name":"Brooks I. Mitchell","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:02:12.215092Z","pmid":"38949728","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":[]}