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.

S.Dzanibe A. J. Wilk S. Canny T. Ranganath B. Alinde F. Rubelt H. Huang M. Davis S. P. Holmes H. B. Jaspan C. A. Blish C. M. Gray

S.Dzanibe A. J. Wilk S. Canny ...+8 C. M. Gray

摘要

With increasing success of preventing vertical HIV transmission, there are an increased number of HIV-exposed uninfected infants (iHEU), who have an elevated risk of infections throughout infancy relative 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 V{beta} 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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