Disrupted Memory T Cell Expansion in HIV-exposed Uninfected Infants is Preceded by Premature Skewing of T Cell Receptor Clonality

Overview

Journal bioRxiv

Date 2023 Jun 9

PMID 37292866

Authors

Sonwabile Dzanibe

Aaron J Wilk

Susan Canny

Thanmayi Ranganath

Berenice Alinde

Florian Rubelt

Huang Huang

Mark M Davis

Susan Holmes

Heather B Jaspan

Catherine A Blish

Clive M Gray

Affiliations

Soon will be listed here.

Abstract

While preventing vertical HIV transmission has been very successful, the increasing number of HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Immune developmental differences between iHEU and iHUU remains poorly understood and here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations and differences in the emergence of NK cell populations and T cell memory differentiation between iHEU and iHUU. Specific NK cells observed at birth were also predictive of acellular pertussis and rotavirus vaccine-induced IgG and IgA responses, respectively, at 3 and 9 months of life. T cell receptor Vβ clonotypic diversity was significantly and persistently lower in iHEU preceding the expansion of T cell memory. Our findings show that HIV/ARV exposure disrupts innate and adaptive immunity from birth which may underlie relative vulnerability to infections.

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