Slow progression of pediatric HIV associates with early CD8 + T cell PD-1 expression and a stem-like phenotype
Vieira, Vinicius (Department of Paediatrics, University of Oxford)
Lim, Nicholas (Department of Paediatrics, University of Oxford)
Singh, Alveera (Africa Health Research Institute)
Leitman, Ellen (Department of Paediatrics, University of Oxford)
Dsouza, Reena (Department of Paediatrics, University of Oxford)
Adland, Emily (Department of Paediatrics, University of Oxford)
Muenchhoff, Maximilian (German Center for Infection Research)
Roider, Julia (Department of Infectious Diseases, Ludwig-Maximilians-University)
Marin Lopez, Miguel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Carabelli, Julieta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Giandhari, Jennifer (KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal)
Groll, Andreas (Department of Statistics, TU Dortmund University)
Jooste, Pieter (Department of Paediatrics, Kimberley Hospital)
Prado, Julia G. (Institut Germans Trias i Pujol)
Thobakgale, Christina (University of KwaZulu-Natal)
Dong, Krista (Ragon Institute of MGH, MIT and Harvard (Estats Units d'Amèrica))
Kiepiela, Photini (Wits Health Consortium, Johannesburg)
Prendergast, Andrew J. (Zvitambo Institute for Maternal and Child Health Research)
Tudor-Williams, Gareth (Imperial College London. Centre for Paediatrics and Child Health)
Frater, John (Oxford NIHR Biomedical Research Centre)
Walker, Bruce D. (Ragon Institute of MGH, MIT and Harvard)
Ndung'u, Thumbi (University College London. Division of Infection and Immunity)
Ramsuran, Veron (Centre for the AIDS Programme of Research in South Africa)
Leslie, Alasdair (School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal)
Kløverpris, Henrik N. (Department of Immunology and Microbiology, University of Copenhagen)
Goulder, Philip (Doris Duke Medical Research Institute, University of KwaZulu-Natal)
Universitat Autònoma de Barcelona

Fecha:	202
Resumen:	HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. 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 before ATI was the main predictor of slow progression during ATI. PD-1 + CD8 + T cell frequency was also negatively correlated with CCR5 and HLA-DR 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 pediatric progressors and viremic adults had a terminally exhausted PD-1 + CD39 + population. TCF-1 + PD-1 + expression on CD8 + T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted 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 infants who received early ART with a preserved and nonexhausted T cell compartment.
Ayudas:	Ministerio de Economía y Competitividad RD16/0025/0041
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	AIDS/HIV ; Immunology ; Adaptive immunity ; T cells
Publicado en:	JCI Insight, Vol. 8 (february 2023) , ISSN 2379-3708

DOI: 10.1172/jci.insight.156049
PMID: 36602861

15 p, 5.1 MB

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