ArticlePloS one2015
Cerebrospinal fluid (CSF) CD8+ T-cells that express interferon-gamma contribute to HIV associated neurocognitive disorders (HAND).
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 3 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Association between cerebrospinal fluid CXCL10 and neurocognitive disorders in people living with HIV: a meta-analysis.AIDS research and therapy · 2025Pooled it
- The relationship between HIV-1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post-mortem brain tissue.Reviews in medical virology · 2024Pooled it
- Implications and prospects of immunological and neuroimaging research in HIV-associated neurocognitive disorders.Frontiers in neurologyPooled it
- Smoldering in the sanctuary: HIV-associated brain injury in the ART era.The Journal of clinical investigation · 2026Review
- MSC transplantation ameliorates depression in lupus by suppressing Th1 cell-shaped synaptic stripping.JCI insight · 2025Article
- Antiretroviral drug therapy does not reduce neuroinflammation in an HIV-1 infection brain organoid model.Journal of neuroinflammation · 2025Article
- Dynamics of peripheral T cell exhaustion and monocyte subpopulations in neurocognitive impairment and brain atrophy in chronic HIV infection.Journal of neurovirology · 2024Article
- Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024Review
- Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.Life (Basel, Switzerland) · 2024Review
- The role of interferon signaling in neurodegeneration and neuropsychiatric disorders.Frontiers in psychiatry · 2024Review
- Article
- Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.Journal of neurovirology · 2023Article
- Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders.Frontiers in immunology · 2023Article
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV.Brain, behavior, & immunity - health · 2022Article
- Aberrant Synaptic Pruning in CNS Diseases: A Critical Player in HIV-Associated Neurological Dysfunction?Cells · 2022Review
- Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B.Journal of neurovirology · 2022Article
- Article
- Soluble Biomarkers of Cognition and Depression in Adults with HIV Infection in the Combination Therapy Era.Current HIV/AIDS reports · 2021Review
- Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis.
methodsTo investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART.
resultsData were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/μl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF.
conclusionsPresence of IFNγ expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.