Extreme prematurity and sepsis strongly influence frequencies and functional characteristics of circulating γδ T and natural killer cells

Abstract

Objectives Extremely 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. Methods Peripheral 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. Results Extreme 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. Conclusion Prematurity strongly influences the levels of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life.

Effects of extremely preterm birth on cytokine and chemokine responses induced by T‐cell activation during infancy

“…In this trial, L. reuteri supplementation did not significantly affect immune development. This is consistent with our previous finding in the same cohort, where we did not observe any phenotypic changes of the conventional 16 or unconventional 15 T-cell compartment. It is important to note that the lack of effects of L. reuteri on induced T-cell response in peripheral blood does not rule out a local immunological impact on the small intestine, where probiotics are more likely to exert their effects.…”

“…14 We have previously observed notable differences in T-cell frequencies in EPT infants, with several differences that persisted up to Gw36. 15,16 However, the functional capacity of T cells to respond to activating signals has yet to be determined in EPT infants. [17][18][19] The composition of the gut microbiota during the initial months after birth critically influences immune maturation, 20 and an impaired gut microbiota development has been observed in preterm infants.…”

“…While some differences in immune responses between preterm and term infants resolve with age, 13 certain immune discrepancies may not be alleviated but further exacerbated 3 months after birth 14 . We have previously observed notable differences in T‐cell frequencies in EPT infants, with several differences that persisted up to Gw36 15,16 . However, the functional capacity of T cells to respond to activating signals has yet to be determined in EPT infants 17–19 …”

Role of innate T cells in necrotizing enterocolitis

“…In the subsequent 2-3 weeks, however, that higher proportion of NKT cells decreases to a level similar to that of full-term infants. This is likely due to gestational development because the proportion of CD3 + T cells expands and positively correlates with gestational age ( 52 ). The proportion of NKT cells in the blood should expand as infants grow older since the proportion of NKT cells in adult blood is much higher than that in cord blood ( 45 ).…”

“…Data on how gestational age impacts MAIT cell levels is conflicting. One study suggests that the proportion of neonatal MAIT cells is low and does not seem to be affected by gestational age ranged 23 to 28 weeks ( 52 ). However, another study using cord blood from broader range of gestational ages (24 weeks to full term) showed that the proportion of MAIT cells in CD3 + T cells negatively correlated with gestational age ( 36 ).…”