Immune systems of preemies can catch up

According to a new study published in March 2020 in the journal Nature Communications, babies born prematurely up to 32 weeks of pregnancy can quickly catch up on their immune system function after birth, bringing them to a state comparable to term infants.

Preterm infants account for 11% of all live births worldwide. However, these infants are born with immature immune systems, both innate and adaptive. As a result, they often die or suffer because of infections and complications of such infections.

Premature neonate in an incubator. Image Credit: Pushba / Shutterstock
Premature neonate in an incubator. Image Credit: Pushba / Shutterstock

Over a third of all deaths among newborn babies occur in preterm infants, over a million a year. In Australia, about 3% of these deaths are due to infection, but most of these (70% or more) are in babies born preterm.

As a result, there is much interest in knowing how the immune system develops in preterm babies and how environmental cues can accelerate their maturation. Nonetheless, scientists don’t understand much about this area yet.

An earlier study by some of the same researchers showed that when stimulated, CD4+ T cells taken from 2-5 week old preterm babies generated lower levels of interferon-gamma but higher levels of CXCL8 in a subset of babies who were later diagnosed with infection, compared to adults. Surprisingly, term babies also showed the same kind of change.

CXCL8 also enhances the expression of interferon-gamma in specific T cells, which may indicate its immunoprotective and pro-inflammatory function. This earlier finding conflicts with the earlier view that neonatal lymphocytes play an anti-inflammatory role, unlike in adults. In some preemies who developed an infection, the number of T immune cells that produced CXCL-8 was deficient at birth.

This suggests that this could be a marker for premature babies who are at a higher risk of infection in the early part of their lives following birth. There were small differences that were sex-dependent. This could help explain in part why preterm male babies often do worse than their female counterparts.

On the other hand, CD4+ cells can be stimulated via T cell receptors with a Toll-like receptor and specific other receptors to produce CXCL8 in newborns but not in adults. This is just one of the differences in the way the newborn immune system functions compared to the adult.

This kind of knowledge could help prevent infectious complications and improve the outcomes for preemies. For instance, this T cell effector function could be the cause of life-threatening illnesses of the newborn, such as necrotizing enterocolitis. Effector T cells could also be targeted for vaccine development.

The study

In the current study, the investigators looked at babies born too early, before 32 weeks. They analyzed the numbers of various types of immune cells, how they functioned, their state of dormancy or activity, and how they altered after birth. They also examined stool samples to understand the composition of the gut bacteria.

The results

All the infants, though born at different weeks of pregnancy, showed the same kind of changes. The least mature infants, born at 28 weeks, showed a faster rate of change compared to those born later. This indicates that there is a kind of deadline towards which both preterm and term infants move in their development and that the pattern of immune maturation follows a defined pattern following birth.

Implications

Researcher Deena Gibbons says, “These data highlight that the majority of immune development takes place after birth and, as such, even those babies born very prematurely have the ability to develop a normal immune system. We are continuing to study the role of the CXCL8-producing T cell and how it can be activated to help babies fight infection. We also want to take a closer look at other immune functions that change during infection to help improve outcomes for this vulnerable group.”

Journal reference:

Gibbons, D., Fleming, P., Virasami, A. et al. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants. Nat Med 20, 1206–1210 (2014). https://doi.org/10.1038/nm.3670

Dr. Liji Thomas

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Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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