T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy

JCI Insight
Kristin M ScheibleGloria S Pryhuber

Abstract

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31-TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associ...Continue Reading

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Citations

Jul 2, 2019·Journal of Leukocyte Biology·Adam J FikeAlison J Carey
Dec 6, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Khaleda Rahman QaziEva Sverremark-Ekström
Jan 14, 2020·Annual Review of Immunology·Brian D Rudd
Oct 3, 2020·The FEBS Journal·Daniel CostaRobert Castelo
Feb 9, 2021·Frontiers in Immunology·Eleanor C SemmesGenevieve G Fouda
Feb 9, 2021·Frontiers in Immunology·Soumyaroop BhattacharyaThomas J Mariani
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·David J TophamAndrea Sant
Feb 14, 2021·Pediatric Pulmonology·Eli RhoadsClement L Ren
Mar 30, 2021·Current Pediatrics Reports·Emma Idzikowski, Thomas J Connors
May 6, 2021·Journal of Clinical and Translational Science·Andrew McDavidJeanne Holden-Wiltse
Sep 2, 2021·Clinical & Translational Immunology·Lakshanie C WickramasingheMargaret L Hibbs

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Methods Mentioned

BETA
flow cytometry
FCS
Assay

Software Mentioned

Tree Star
LabKey Server
Flowjo
SAS
PROP
REDCap
BD FACS Diva
Research Electronic Data Capture ( REDCap )
Bio Informatics Server
GraphPad Prism

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