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

Autor: Vieira V; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Lim N; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Singh A; Africa Health Research Institute, Durban, South Africa., Leitman E; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Dsouza R; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Adland E; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Muenchhoff M; Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.; German Center for Infection Research, Munich, Germany., Roider J; German Center for Infection Research, Munich, Germany.; Department of Infectious Diseases, Ludwig-Maximilians-University, Munich, Germany., Marin Lopez M; IrsiCaixa AIDS Research Institute, Badalona, Spain., Carabelli J; IrsiCaixa AIDS Research Institute, Badalona, Spain., Giandhari J; KwaZulu-Natal Research Innovation and Sequencing Platform, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Groll A; Department of Statistics, TU Dortmund University, Dortmund, Germany., Jooste P; Department of Paediatrics, Kimberley Hospital, Kimberley, South Africa., Prado JG; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Germans Trias i Pujol Research Institute, Badalona, Spain; Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain., Thobakgale C; Faculty of Health Sciences, Centre for HIV and STIs, National Institute for Communicable Diseases, University of the Witwatersrand, Johannesburg, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Dong K; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA., Kiepiela P; South African Medical Research Council, Durban, South Africa.; Wits Health Consortium, Johannesburg, South Africa., Prendergast AJ; Blizard Institute, Queen Mary University of London, London, United Kingdom.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe., Tudor-Williams G; Centre for Paediatrics and Child Health, Imperial College London, London, United Kingdom., Frater J; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom., Walker BD; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA., Ndung'u T; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.; Division of Infection and Immunity, University College London, London, United Kingdom., Ramsuran V; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa., Leslie A; Africa Health Research Institute, Durban, South Africa.; Division of Infection and Immunity, University College London, London, United Kingdom.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa., Kløverpris HN; Africa Health Research Institute, Durban, South Africa.; Division of Infection and Immunity, University College London, London, United Kingdom.; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Goulder P; Department of Paediatrics, University of Oxford, Oxford, United Kingdom.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2023 Feb 08; Vol. 8 (3). Date of Electronic Publication: 2023 Feb 08.
DOI: 10.1172/jci.insight.156049
Abstrakt: 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.
Databáze: MEDLINE