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Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

Adriano Vieira, Vinicius; Lim, Nicholas; Singh, Alveera; Leitman, Ellen; D'Souza, Reena R; Adland, Emily; Muenchhoff, Maximilian; ... Goulder, Philip; + view all (2023) Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype. JCI Insight , 8 (3) , Article e156049.. 10.1172/jci.insight.156049. Green open access

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Abstract

HIV non-progression despite persistent viraemia is rare among antiretroviral therapy (ART)-naïve adults, but relatively common among ART-naïve children. Previous studies indicate that ART-naïve paediatric slow-progressors (PSPs) adopt immune evasion strategies similar to those described in the SIV natural hosts. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T-cells immediately prior to ATI was the main predictor of slow progression during ATI (r=0.77, p=0.002). PD-1+ CD8+ T-cell frequency was also negatively correlated with CCR5 (r=-0.74, p=0.005) and HLA-DR (r=-0.63, p=0.02) expression on CD4+ T-cells and predicted stronger HIV-specific T-lymphocyte responses. In the CD8+ T-cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas paediatric progressors and viraemic adults were populated with a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T-cells was associated with higher proliferative activity (r=0.41, p=0.03) and stronger Gag-specific effector functionality. These data prompt the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in early-ART-treated infants with a preserved and non-exhausted T-cell compartment.

Type: Article
Title: Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/jci.insight.156049
Publisher version: https://doi.org/10.1172/jci.insight.156049
Language: English
Additional information: Copyright © 2023 Vieira et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: AIDS/HIV, Adaptive immunity, Immunology, T cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10162974
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