Title

Disease Progression in Children with Perinatal HIV Correlates with Increased PD-1+ CD8 T Cells that Coexpress Multiple Immune Checkpoints.

Document Type

Article

Publication Date

11-15-2021

Publication Title

The Journal of infectious diseases

Keywords

JGM

JAX Source

J Infect Dis 2021 Nov 15; 224:1785-95

Volume

224

First Page

1785

Last Page

1795

ISSN

1537-6613

PMID

33864071

DOI

https://doi.org/10.1093/infdis/jiab204

Abstract

BACKGROUND: PD-1 marks exhausted T cells, with weak effector functions. Adults living with 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 (IC) 2B4, CD160 and TIM3, correlates with immune activation and HIV disease progression and HIV-specific and non-specific 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 this subset is functionally exhausted.

CONCLUSION: Children with perinatal HIV have high 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.

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