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

Author:

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

Abstract

AbstractWhile 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 CD56loCD16loPerforin+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.

Funder

U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development

Wellcome Trust

South African Medical Research Council

Fogarty International Training Center

Publisher

Springer Science and Business Media LLC

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