Extremely Preterm Infants Have Significant Alterations in Their Conventional T Cell Compartment during the First Weeks of Life

Abstract

Extremely preterm neonates are particularly susceptible to infections, likely because of severely impaired immune function. However, little is known on the composition of the T cell compartment in early life in this vulnerable population. We conducted a comprehensive phenotypic flow cytometry-based longitudinal analysis of the peripheral conventional T cell compartment of human extremely low gestational age neonates (ELGAN) with extremely low birth weight (ELBW; <1000 g) participating in a randomized placebo-controlled study of probiotic supplementation. PBMCs from ELGAN/ELBW neonates were collected at day 14, day 28, and postmenstrual week 36. Comparisons were made with full-term 14-d-old neonates. Total CD4 + and CD8 + T cell frequencies were markedly lower in the preterm neonates. The reduction was more pronounced among the CD8 + population, resulting in an increased CD4/CD8 ratio. The preterm infants were also more Th2 skewed than the full-term infants. Although the frequency of regulatory T cells seemed normal in the ELGAN/ELBW preterm neonates, their expression of the homing receptors a4b7, CCR4, and CCR9 was altered. Notably, ELGAN/ELBW infants developing necrotizing enterocolitis before day 14 had higher expression of CCR9 in CD4 + T cells at day 14. Chorioamnionitis clearly associated with reduced T regulatory cell frequencies and functional characteristics within the preterm group. Finally, probiotic supplementation with Lactobacillus reuteri did not impose any phenotypic changes of the conventional T cell compartment. In conclusion, notable immaturities of the T cell compartment in ELGAN/ELBW neonates may at least partially explain their increased susceptibility to severe immunemediated morbidities.

Indole-3-Carbinol–Dependent Aryl Hydrocarbon Receptor Signaling Attenuates the Inflammatory Response in Experimental Necrotizing Enterocolitis

“…This observed limited T cell response may be attributed to the limited expansion and differentiation of T cells, including regulatory T cells, in neonatal mice ( 55 , 56 ). Notably, immaturity of the T cell compartment is also observed in extremely preterm human infants, increasing their susceptibility to infection and impairing their immune functions, which may predispose them to NEC development ( 57 ).…”

Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health

“…, blood, lymphoid, and mucosal tissues) has been underexplored. Tregs likely regulate appropriate local mucosal immune responses during microbial colonization, as Tregs may protect against necrotizing enterocolitis in preterm infants by promoting tolerance during newborn gut microbial colonization ( 46 ). Because the immunosuppressive effects of these Tregs may increase infectious disease susceptibility and could dampen vaccine responsiveness in infancy, further research is crucial to gain a deeper understanding of their abundance and function in early life.…”

Dysregulated Mucosal Immunity and Associated Pathogeneses in Preterm Neonates

“…There are several features of preterm T cells which limit their function. First, preterm neonates have been found to have marked lymphopenia (up to 50% reduction) with a significant decrease in the percentage of total, CD4 + , and CD8 + lymphocytes compared with full term infants (121). The reduction is most notable among the CD8 + population, resulting in an increased CD4/CD8 ratio.…”

“…The transcription factors T-bet, GATA3, and RORγt, regulate differentiation into Th1, Th2, and Th17 phenotypes, respectively. Accordingly, recent studies have shown that the proportion of T-bet expressing CD4 + T cells is reduced within the preterm T cell population (121).…”