Disrupted memory T cell expansion in HIV-exposed uninfected infants is preceded by premature skewing of T cell receptor clonality

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

doi:10.1101/2023.05.19.540713

Disrupted memory T cell expansion in HIV-exposed uninfected infants is preceded by premature skewing of T cell receptor clonality

bioRxiv [Preprint]. 2023 May 24:2023.05.19.540713. doi: 10.1101/2023.05.19.540713.

Authors

Sonwabile Dzanibe¹, Aaron J Wilk², Susan Canny^{2

3}, Thanmayi Ranganath², Berenice Alinde^{1

4}, Florian Rubelt^{5

6}, Huang Huang^{5

6}, Mark M Davis^{5

6

7}, Susan Holmes⁸, Heather B Jaspan^{1

9}, Catherine A Blish^{2

6

10}, Clive M Gray^{1

4}

Affiliations

¹ Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
² Department of Medicine, School of Medicine, Stanford University, Stanford, CA.
³ Division of Rheumatology, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA USA.
⁴ Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
⁵ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Howard Hughes Medical Institute, School of Medicine, Stanford University, Stanford, CA.
⁸ Department of Statistics, Stanford University, Stanford, CA, USA.
⁹ Seattle Children's Research Institute and Department of Paediatrics and Global Health, University of Washington, Seattle, WA.
¹⁰ Chan Zuckerberg Biohub, San Francisco, CA.

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.

Keywords: HIV exposure; NK cels and antibody responses; T cell receptor; infant immunity.

Publication types

Preprint

Abstract

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