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

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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; + 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 α4β7, 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 immune-mediated morbidities. Key Points ELGAN/ELBW neonates are lymphopenic and their T cells have altered homing capacity. ELGAN/ELBW infants with chorioamnionitis have an altered Treg population.

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