Alterations in Regulatory T Cell Subpopulations Seen in Preterm Infants

Abstract

Regulatory T cells are a population of CD4+ T cells that play a critical role in peripheral tolerance and control of immune responses to pathogens. The purpose of this study was to measure the percentages of two different regulatory T cells subpopulations, identified by the presence or absence of CD31 (Recent thymic emigrants and peripherally induced naïve regulatory T cells), in term and preterm infant cord blood. We report the association of prenatal factors, intrauterine exposure to lipopolysaccharide and inflammation and the percentages of these regulatory T cell subpopulations in term and preterm infants. Cord blood samples were collected from both term and preterm infants and mononuclear cells isolated over a Ficoll-Hypaque cushion. Cells were then stained with fluorochrome-labeled antibodies to characterize regulatory T cell populations and analyzed with multi-color flow cytometry. Cord blood plasma C-reactive protein, and lipopolysaccharide were also measured. Placental pathology was also examined. We report a gestational age-dependent difference in the percentage of total regulatory T cells, in which preterm infants of lower gestational ages have an increased percentage of regulatory T cells. We report the presence of two populations of regulatory T cells (CD31+ and CD31-) in cord blood of term and preterm infants and their association with different maternal and fetal characteristics. Factors associated with differences in the percentage of CD31- Tregs included the use of prenatal antibiotics, steroids and magnesium sulfate. In addition, the percentage of CD31- Tregs was significantly higher in cord blood of preterm pregnancies associated with inflammation and prenatal lipopolysaccharide exposure. The peripheral Treg pool of preterm infants could be altered by prenatal exposure to inflammation and chorioamnionitis; however, the clinical implications of this finding are not yet understood.

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

“…Characterization of IL-17 + cells will be warranted in future studies of chorio-exposed neonates. Some limitations of our approach are the low number of subjects enrolled in our functional experiment, and the fact that magnesium sulfate usage, which has recently been associated with Treg phenotypic alterations (such as the percentage of CD31 + Treg) was not recorded [54]. Future studies will be needed to clarify potential differences between Treg from mild and severe chorio and the effect magnesium sulfate treatment.…”

Determinants of early life immune responses to RSV infection

“…Immunosuppressive plasma factors such as adenosine and anti-inflammatory cytokines dampen inflammatory responses, and transforming growth factor beta (TGFβ) has been found to mediate suppression of natural killer (NK) cell function. Tregs, one potential source of TGFβ, have been found in higher numbers in newborns and preterm infants and possess immunosuppressive functions during early life [15,16]. Another cellular source of immunosuppression, CD71+ erythroid cells, are prevalent during early life and may compromise host defenses [17].…”

Reference Intervals of Platelets, Lymphocytes and Cardiac Biomarkers in Umbilical Cord Blood

“…Preterm infants are highly susceptible to invasive infections, which are leading causes of mortality and longterm morbidity. Treg levels and gestational age inversely correlated in several studies [48][49][50]. Preterm infants have higher Treg levels than full-term newborns.…”

“…The T cell immune response in preterm infants is supposed to be dysregulated and afected by prenatal factors including intrauterine inlammation and maternal characteristics. This dysregulation of T cell immunity could lead to inefective clearance of pathogens [49]. Tregs have two populations (CD31 + and CD31 -), and the ratio alteration of these populations is associated with diferent intra-and/or extra-uterine milieu.…”