Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants.
Sonwabile DzanibeAaron J WilkSusan CannyThanmayi RanganathBerenice AlindeFlorian RubeltHuang HuangMark M DavisSusan P HolmesHeather B JaspanCatherine A BlishClive M GrayPublished in: Nature communications (2024)
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 lo CD16 lo Perforin + 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.
Keyphrases
- hiv infected
- antiretroviral therapy
- hiv positive
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- nk cells
- rheumatoid arthritis
- south africa
- clinical trial
- working memory
- single cell
- systemic lupus erythematosus
- pregnant women
- randomized controlled trial
- high glucose
- endothelial cells
- wastewater treatment
- idiopathic pulmonary fibrosis