Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints.

Autor:	Tailor J; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Foldi J; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Generoso M; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., McCarty B; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Alankar A; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Kilberg M; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Mwamzuka M; Bomu Hospital, Mombasa, Kenya., Marshed F; Bomu Hospital, Mombasa, Kenya., Ahmed A; Bomu Hospital, Mombasa, Kenya., Liu M; Department of Population Health, New York University School of Medicine, New York, New York, USA., Borkowsky W; Division of Infectious Diseases, Department of Pediatrics, New York University School of Medicine, New York, New York, USA., Unutmaz D; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA., Khaitan A; Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2021 Nov 22; Vol. 224 (10), pp. 1785-1795.
DOI:	10.1093/infdis/jiab204
Abstrakt:	Background: PD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV. Methods: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses. Results: PD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3- in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted. Conclusions: Children with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1-directed immunotherapies for pediatric HIV remission and cure. (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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