Abstract

Preterm infants born before 32 weeks gestational age (GA) have high rates of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) despite recent improvements in infection control and nutrition. Breast milk has a clear protective effect against both these outcomes likely due to multiple mechanisms which are not fully understood but may involve effects on both the infant's immune system and the developing gut microbiota. Congregating at the interface between the mucosal barrier and the microbiota, innate and adaptive T lymphocytes (T cells) participate in this interaction but few studies have explored their development after preterm delivery. We conducted a literature review of T cell development that focuses on fetal development, postnatal maturation and the influence of milk diet. The majority of circulating T cells in the preterm infant display a naïve phenotype but are still able to initiate functional responses similar to those seen in term infants. T cells from preterm infants display a skew toward a T-helper 2(Th2) phenotype and have an increased population of regulatory cells (Tregs). There are significant gaps in knowledge in this area, particularly in regards to innate-like T cells, but work is emerging: transcriptomics and mass cytometry are currently being used to map out T cell development, whilst microbiomic approaches may help improve understanding of events at mucosal surfaces. A rapid rise in organoid models will allow robust exploration of host-microbe interactions and may support the development of interventions that modulate T-cell responses for improved infant health.

Highlights

  • Especially before 32 weeks gestational age (GA) are susceptible to diseases associated with invasive bacterial infections, late onset sepsis (LOS) and necrotizing enterocolitis (NEC)

  • Preterm infants have a T cell population that was designed for fetal life and differs systematically from term infants (Table 1)

  • regulatory T cells (Tregs) protect the preterm infant from an excessive innate response which may reduce the risk of NEC but may increase the risk of LOS

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Summary

INTRODUCTION

Especially before 32 weeks gestational age (GA) are susceptible to diseases associated with invasive bacterial infections, late onset sepsis (LOS) and necrotizing enterocolitis (NEC). These occur in around 30 and 6% of very preterm infants, respectively, according to recent data [1], most occur in the first 4 weeks of life, and both diseases are associated with changes in the gut microbiota [2, 3]. T lymphocytes (T cells) are an important component of the immune response to infection, this role is balanced against their emerging role in tissue regeneration and repair. Relative abundance (preterm compared to term infants, population as % of T cells)

SUPPRESSION OF THE IMMUNE RESPONSE
DIETARY INTERACTIONS WITH MUCOSAL T CELLS
Translocation of Milk Derived Immune Cells
Findings
CONCLUSION
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