Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

Sonwabile Dzanibe; Aaron J Wilk; Susan Canny; Thanmayi Ranganath; Berenice Alinde; Florian Rubelt; Huang Huang; Mark M Davis; Susan P Holmes; Heather B Jaspan; Catherine A Blish; Clive M Gray

doi:10.1038/s41467-024-47955-5

Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

Nat Commun. 2024 May 14;15(1):4080. doi: 10.1038/s41467-024-47955-5.

Authors

Sonwabile Dzanibe^{1

2}, Aaron J Wilk³, Susan Canny^{3

4}, Thanmayi Ranganath³, Berenice Alinde⁵, Florian Rubelt^{6

7}, Huang Huang⁷, Mark M Davis^{6

7

8}, Susan P Holmes⁹, Heather B Jaspan^{10

11

12}, Catherine A Blish^{13

14

15}, Clive M Gray^{16

17}

Affiliations

¹ Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
² Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³ Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
⁴ Division of Rheumatology, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
⁵ Division of Immunology, Department of Biomedical Sciences, Biomedical Research Institute, Stellenbosch University, Cape Town, South Africa.
⁶ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Howard Hughes Medical Institute, School of Medicine, Stanford University, Stanford, CA, USA.
⁹ Department of Statistics, Stanford University, Stanford, CA, USA.
¹⁰ Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. hbjaspan@gmail.com.
¹¹ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. hbjaspan@gmail.com.
¹² Seattle Children's Research Institute and Department of Paediatrics and Global Health, University of Washington, Seattle, WA, USA. hbjaspan@gmail.com.
¹³ Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA. cblish@stanford.edu.
¹⁴ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA. cblish@stanford.edu.
¹⁵ Chan Zuckerberg Biohub, San Francisco, CA, USA. cblish@stanford.edu.
¹⁶ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. cgray@sun.ac.za.
¹⁷ Division of Immunology, Department of Biomedical Sciences, Biomedical Research Institute, Stellenbosch University, Cape Town, South Africa. cgray@sun.ac.za.

Abstract

While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). 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 in T cell memory differentiation between iHEU and iHUU being significant from week 15 of life. The altered memory T cell differentiation in iHEU was preceded by lower TCR Vβ clonotypic diversity and linked to TCR clonal depletion within the naïve T cell compartment. Compared to iHUU, iHEU had elevated CD56^loCD16^loPerforin⁺CD38⁺CD45RA⁺FcεRIγ⁺ NK cells at 1 month postpartum and whose abundance pre-vaccination were predictive of vaccine-induced pertussis and rotavirus antibody responses post 3 months of life. Collectively, HIV/ARV exposure disrupted the trajectory of innate and adaptive immunity from birth which may underlie relative vulnerability to infections in iHEU.

MeSH terms

Adaptive Immunity / immunology
Cell Differentiation / immunology
Female
HIV Infections* / immunology
HIV Infections* / virology
Humans
Immunologic Memory*
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical*
Killer Cells, Natural / immunology
Longitudinal Studies
Male
Memory T Cells / immunology
Receptors, Antigen, T-Cell / immunology
Receptors, Antigen, T-Cell / metabolism

Substances

Receptors, Antigen, T-Cell

Abstract

MeSH terms

Substances

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