Journal article
HIV-1 controllers possess a unique CD8+ T cell activation phenotype and loss of control is associated with increased expression of exhaustion markers
PloS one, v 20(8), e0328706
01 Aug 2025
PMID: 40875618
Abstract
BackgroundHIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.ResultsWe explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control by examining immune characteristics of HIV-1 persistent controllers and transient controllers who lost control within the duration of the study. Using flow cytometry, we analyzed exhaustion marker expression on CD8+ T cells from HIV-1 controllers and determined that they maintain a unique exhaustion profile as compared to people without HIV-1 and HIV-1 standard progressors. The low level of T cell exhaustion seen in HIV-1 controllers was reversed when these individuals lost control and showed increased viral loads. Combinatorial immune checkpoint blockade targeting exhaustion markers was able to restore ex vivo control in CD8+ T cells from former controllers.ConclusionsThese results suggest that CD8+ T cell exhaustion compromises the ability to control viral replication in HIV-1 controllers. The character of exhaustion in response to HIV-1 and therapy is distinct in HIV-1 persistent controllers, transient controllers and standard progressors.
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Details
- Title
- HIV-1 controllers possess a unique CD8+ T cell activation phenotype and loss of control is associated with increased expression of exhaustion markers
- Creators
- Angel Lin - Drexel UniversityRachel Van Duyne - Drexel UniversityStephen SmithZachary Klase - Drexel University
- Publication Details
- PloS one, v 20(8), e0328706
- Publisher
- Public Library of Science (PLOS)
- Number of pages
- 24
- Grant note
- Drexel UniversityNIH from the National Institute on Drug Abuse: NIH/NIDA R01-DA057337, NIH/NIDA DP2-DA044550
Funding for this work came from Drexel University internal funds to ZK, and NIH grants NIH/NIDA R01-DA057337 and NIH/NIDA DP2-DA044550 to ZK from the National Institute on Drug Abuse-https://nida.nih.gov/The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; Obstetrics and Gynecology
- Web of Science ID
- WOS:001560804400035
- Scopus ID
- 2-s2.0-105014267583
- Other Identifier
- 991022084531004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology