Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis

Abstract

SummaryThe predisposition of preterm neonates to invasive infection is, as yet, incompletely understood. Regulatory T cells (T regs ) are potential candidates for the ontogenetic control of immune activation and tissue damage in preterm infants. It was the aim of our study to characterize lymphocyte subsets and in particular CD41 CD25 1 forkhead box protein 3 (FoxP3) 1 T regs in peripheral blood of well-phenotyped preterm infants (n 5 117; 23 1 0 -36 1 6 weeks of gestational age) in the first 3 days of life in comparison to term infants and adults. We demonstrated a negative correlation of T reg frequencies and gestational age. T regs were increased in blood samples of preterm infants compared to term infants and adults. Notably, we found an increased T reg frequency in preterm infants with clinical early-onset sepsis while cause of preterm delivery, e.g. chorioamnionitis, did not affect T reg frequencies. Our data suggest that T regs apparently play an important role in maintaining maternal-fetal tolerance, which turns into an increased sepsis risk after preterm delivery. Functional analyses are needed in order to elucidate whether T regs have potential as future target for diagnostics and therapeutics.

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period

“…During pregnancy, the immune system predominantly exhibits tolerogenic features that protect the fetus from maternal rejection; postnatally, however, these features may predispose to infections [6,9]. Potential mechanisms of postnatal immunosuppression are a bias of T helper (Th) cell responses towards Th2 and an accumulation of immunemodulatory cells such as regulatory T cells (T regs ), regulatory B cells (B regs ) and CD71 positive erythroid cells [7,10,11]. Recently, we and others have described myeloidderived suppressor cells (MDSC) as potential immune regulators during pregnancy [12][13][14][15].…”

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

“…Especially, Tregs in UCB may contribute to maintain the immune homeostasis in the feto-maternal relationship, and the presence of Tregs would be essential to prevent immune dysregulation in fetus and neonates [17,44]. [45,46].…”

“…Early-onset septic infants have signiicantly higher Treg frequencies than infants without early-onset sepsis. The increased Treg level may cause an uncontrolled immunosuppression and therefore results in an increased risk of sepsis for the preterm infants especially for the most vulnerable very low-birth-weight infants (Figure 1) [46].…”

Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular energy metabolism in preterm newborns

“…This serves to minimize the immunopathology of energetically costly inflammatory responses and instead to use energy for maintenance of organ functions . These phenomena explain the inverse correlation between the frequency of blood regulatory T cells (Treg) and gestational age in noninfected preterm infants, and higher blood Treg frequencies in preterm than term infants . The disease tolerance strategy makes infants, especially preterm infants, withstand 10‐100 times greater levels of circulating bacteria, relative to adults .…”

“…5 These phenomena explain the inverse correlation between the frequency of blood regulatory T cells (Treg) and gestational age in noninfected preterm infants, and higher blood Treg frequencies in preterm than term infants. 6,7 The disease tolerance strategy makes infants, especially preterm infants, withstand 10-100 times greater levels of circulating bacteria, relative to adults. 3 This host defense strategy may also explain the emerging evidence of neonatal sepsis to be associated with immunosuppression and increased circulating Treg frequencies.…”