Introduction: There is little knowledge on the immune system of extremely premature infants (born at 24-28 weeks of gestation). This paucity of evidence impedes advances in the fight against bronchopulmonary dysplasia (BPD), a common, severe chronic lung disease that entails significant morbidity and mortality. As no safe and effective treatment exists, there is an urgent need to improve the understanding of preterm immunity and thereby reveal novel therapeutic avenues.
Methods: Blood was collected from extremely preterm infants at 5 timepoints [birth, days 1, 7 and 14 and 36 weeks corrected gestational age (WCGA)]. Following overnight stimulation with PMA/ionomycin, LPS or vehicle in whole blood assays, flow cytometry was used to explore T cells and their polarisation, macrophages and dendritic cells (DC) and their activation status, haematopoietic stem cells and endothelial progenitor cells (EPC). Cells from healthy term infants and adults served as controls.
Results: In the preterm babies, expression of the activation marker MHC II progressively increased over time on macrophages (d1, 48% vs 36 WCGA, 86%) and DC (d1, 24% vs 36 WCGA, 56%). Comparing the one infant that developed BPD with the two that did not at 36 WCGA, we observed a marked increase in macrophage (6-fold) and DC activation (2-fold), but fewer circulating EPC (0.3% vs 1.4% of viable cells). Unexpectedly, we also found that up to 10% of one preterm infant’s CD8+ T-cells were positive for IL-17A and IFN-gamma on d7.
Conclusion: It only took the results from three preterm infants to reveal that this first-of-its-kind study will revolutionise the understanding of preterm immunity; for example, these first data suggest that, contrary to current belief, preterm babies are capable of mounting Th1 and Th17 responses. BPD appears associated with markedly increased cellular activation - a promising finding that, in combination with the pending plasmatic analysis, may provide a basis for therapeutic innovations.