Scheible, Kristin M.Emo, JasonLaniewski, NathanBaran, Andrea M.Peterson, Derick R.Holden-Wiltse, JeanneBandyopadhyay, SanjuktaStraw, Andrew G.Huyck, HeidieAshton, John M.Tripi, Kelly SchoopingArul, KaranWerner, ElizabethScalise, TanyaMaffett, DeannaCaserta, MaryRyan, Rita M.Reynolds, Anne MarieRen, Clement L.Topham, David J.Mariani, Thomas J.Pryhuber, Gloria S.2018-11-192018-11-192018-02-22Scheible, K. M., Emo, J., Laniewski, N., Baran, A. M., Peterson, D. R., Holden-Wiltse, J., Bandyopadhyay, S., Straw, A. G., Huyck, H., Ashton, J. M., Tripi, K. S., Arul, K., Werner, E., Scalise, T., Maffett, D., Caserta, M., Ryan, R. M., Reynolds, A. M., Ren, C. L., Topham, D. J., Mariani, T. J., … Pryhuber, G. S. (2018). T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy. JCI insight, 3(4), e96724. Advance online publication. doi:10.1172/jci.insight.96724https://hdl.handle.net/1805/17790The 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 associate abnormal T cell development with health outcomes in infants.en-USPublisher PolicyAdaptive immunityDevelopmentImmunologyArticle