CD8+ T cell priming is quantitatively but not qualitatively impaired in people with HIV-1 on antiretroviral therapy

Cabral-Piccin, Mariela P., Briceño, Olivia, Papagno, Laura, Liouville, Benjamin, White, Eoghann, Perdomo-Celis, Federico, Autaa, Gaëlle, Volant, Stevenn, Llewellyn-Lacey, Sian, Fromentin, Rémi, Chomont, Nicolas, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Sáez-Cirión, Asier, Lambotte, Olivier, Katlama, Christine and Appay, Victor 2024. CD8+ T cell priming is quantitatively but not qualitatively impaired in people with HIV-1 on antiretroviral therapy. AIDS 38 (2) , pp. 161-166. 10.1097/QAD.0000000000003746 Item availability restricted.

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Abstract

Background: The induction of de novo CD8+ T-cell responses is essential for protective antiviral immunity, but this process is often impaired in people with HIV-1 (PWH). We investigated the extent to which the immune competence of naive CD8+ T cells, a key determinant of priming efficacy, could be preserved or restored in PWH via long-term antiretroviral therapy (ART). Methods: We used flow cytometry, molecular analyses of gene transcription and telomere length, and a fully validated priming assay to characterize naive CD8+ T cells ex vivo and evaluate the induction of antigen-specific effector/memory CD8+ T cells in vitro, comparing age-matched healthy uninfected donors (HUDs), PWH on ART, and natural HIV-1 controllers (HICs). Results: We found that naive CD8+ T cells were numerically reduced and exhibited a trend toward shorter telomere lengths in PWH on ART compared with HUDs and HICs. These features associated with impaired priming efficacy. However, we also found that naive CD8+ T cells were fully equipped proliferatively and transcriptionally in PWH on ART, enabling the generation of antigen-specific effector/memory CD8+ T cells with functional and phenotypic attributes comparable with those primed from HUDs. Conclusion: Our data suggest that naive CD8+ T cells in PWH on ART are intrinsically capable of generating functionally and phenotypically intact effector/memory CD8+ T cells in response to antigen, despite evidence of senescence and an overall numerical reduction that compromises priming efficacy relative to HUDs and HICs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Lippincott, Williams & Wilkins
ISSN:	0269-9370
Date of First Compliant Deposit:	26 October 2023
Date of Acceptance:	14 September 2023
Last Modified:	17 Jan 2024 16:15
URI:	https://orca.cardiff.ac.uk/id/eprint/163516

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