Abstract
ObjectivesExtremely low gestational age neonates with extremely low birthweight (ELGAN/ELBW) are highly susceptible to infection. This is linked to their relatively immature immune system which is not yet fully compatible with an extra‐uterine environment. Here, we performed a longitudinal characterisation of unconventional T and natural killer (NK) cells in ELGAN/ELBW during their first months of life.MethodsPeripheral blood mononuclear cells were collected from 97 ELGAN/ELBW at 14 and 28 days of life and at a time point corresponding to postmenstrual week 36 + 0. γδ T‐cell, NKT‐cell, mucosa‐associated invariant T‐cell and NK cell frequencies and characteristics were analysed by flow cytometry. As control, cells from 14‐day‐old full‐term (FT) infants were included.ResultsExtreme prematurity had significant bearing on γδ T‐cell and NK cell frequencies and characteristics. ELGAN/ELBW had significantly higher proportions of γδ T cells that were skewed towards effector and effector memory phenotypes, characteristics that were maintained throughout the study period. Expression of the gut homing receptor CCR9 was also more common in γδ T cells from ELGAN/ELBW. Conversely, NK cell frequencies were markedly lower and skewed towards a cytotoxic phenotype in the ELGAN/ELBW group at 14 days of age. Culture‐proven sepsis with an onset during the first 14 days after birth further manifested these differences in the γδ T‐ and NK cell populations at 14 days of age.ConclusionPrematurity strongly influences the levels of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life.
Highlights
Preterm birth is a strong risk factor for neonatal disease, long-term complications and death
This was likely to reflect a low percentage of conventional T cells, as both cd Tand NKT-cell frequencies constituted a proportionally large part of the CD3+ T-cell pool in the ELGAN/ELBW compared with FT neonates (Figure 3b and c)
For cd T and NKT cells, the proportions decreased with age (Figure 3l and m), and at week 36, they were proportional to percentages seen in FT neonates (Supplementary table 1)
Summary
Preterm birth is a strong risk factor for neonatal disease, long-term complications and death. While full-term neonates have a relatively welldeveloped immune system,[2] preterm neonates have an impaired ability to combat pathogens, with invasive infection and sepsis as leading causes of morbidity and mortality.[3] This is clearly linked to features of their immune system that is still developing: while it is probably appropriate for their respective developmental stage, it is not fully compatible with an extra-uterine life. Innate lymphocytes such as natural killer (NK), NKT, cd T and mucosa-associated invariant T (MAIT) cells all develop and mature during foetal life, but at different time points. MAIT cells are a highly conserved population of T lymphocytes and represent a very small fraction of cord blood T cells, but can comprise up to 10% of the entire T-cell population in adults.[7,8]
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