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

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

doi:10.1101/2023.05.19.540713

bioRxiv · 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.

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

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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 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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Dzanibe, S., Wilk, A. J., Canny, S., Ranganath, T., Alinde, B., Rubelt, F., Huang, H., Davis, M., Holmes, S. P., Jaspan, H. B., Blish, C. A., Gray, C. M.. 2023-05-20. Disrupted memory T cell expansion in HIV-exposed uninfected infants is preceded by premature skewing of T cell receptor clonality.. https://doi.org/10.1101/2023.05.19.540713

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