Developmentally determined reduction in CD31 during gestation is associated with CD8 + T cell effector differentiation in preterm infants

Scheible, Kristin; Emo, Jason; Yang, Hongmei; Holden‐Wiltse, Jeanne; Straw, Andrew G; Huyck, Heidie; Misra, Sara K.; Topham, David J.; Ryan, Rita M.; Reynolds, Anne Marie; Mariani, Thomas J.; Pryhuber, Gloria S.

doi:10.1016/j.clim.2015.07.003

Cited by 23 publications

(23 citation statements)

References 37 publications

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“…T cells lacking CD31 expression are resistant to tolerance induction . Interestingly, CD31 expression is reduced on late preterm infants (<36 weeks), but gradually increases as the fetus approaches full gestation . In fact, there is a developmentally regulated increase in CD31 expression in preterm neonates over the first 2–3 months of life, as they approach their term‐corrected age .…”

Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

“…83 Interestingly, CD31 expression is reduced on late preterm infants (<36 weeks), but gradually increases as the fetus approaches full gestation. 84 In fact, there is a developmentally regulated increase in CD31 expression in preterm neonates over the first 2-3 months of life, as they approach their term-corrected age. 11 Premature neonates with a decreased abundance of CD31 + CD4 + T cells and more CD31 − CD4 + cells at the time of discharge from the hospital are associated with increased morbidity due to respiratory illnesses potentially driven by excessive TNF production.…”

Section: The Role Of the Human Public Tcr Repertoirementioning

confidence: 99%

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Dissecting the defects in the neonatal CD8+ T-cell response

Fike

Kumova

Carey

2019

Journal of Leukocyte Biology

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The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8+ T cells are critical for the response against intracellular bacteria and viruses, but this immune compartment maintains altered function relative to adult counterparts because of the unique challenges which infants face. Here, we review our current understanding of the factors which may promote the attenuation and altered function of the neonatal CD8+ T‐cell response and potential avenues for future study. Specifically, we have focused on the neonatal CD8+ T‐cell ontogeny, memory formation, TCR structure and repertoire, TCR inhibitory receptors, and the clinical implications of altered neonatal CD8+ T‐cell function. Special emphasis has been placed on examining the response of preterm neonates relative to term neonates and adults.

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Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

Section: The Role Of the Human Public Tcr Repertoirementioning

confidence: 99%

Dissecting the defects in the neonatal CD8+ T-cell response

Fike

Kumova

Carey

2019

Journal of Leukocyte Biology

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“…normal fetal T cell development, to those with postnatal T cell "developmental arrest," we can begin to understand the impact of normal fetal immune development on an infant's health. We have previously shown that ELGANs have fewer CD8 + T cells expressing the inhibitory molecule CD31 and are hyperresponsive when compared with T cells from full-term (FT) infants (7). In their study, including 26 infants, Gibbons et al recently identified the neutrophil chemoattractant IL-8 (CXCL8) as a major effector cytokine produced by CD4 + T cells from neonates born ≤30 weeks after conception and that the majority of IL-8 producers coexpressed CD31 (6).…”

Section: Introductionmentioning

confidence: 99%

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

Scheible¹,

Emo²,

Laniewski³

et al. 2018

JCI Insight

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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 associate abnormal T cell development with health outcomes in infants.

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“…15 Nevertheless, CD31 has come to be widely used as a marker of recent thymic emigrants within the CD4 + CD45RA + T cell population. [15][16][17][18][19][20][21][22] Importantly, temporal regulation of PECAM-1 expression in T cells other than those that are CD4 + CD45RA + has been much less well studied. Early studies reported that, following its down-regulation in response to TCR stimulation, CD31 remains absent from mature CD4 + T cells throughout subsequent maturation events, including establishment of memory (i.e., CD4 + CD45RA − CD45RO + ).…”

mentioning

confidence: 99%

Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8+ T cells

Newman

McOlash

et al. 2018

Journal of Leukocyte Biology

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Inhibitory cell surface proteins on T cells are often dynamically regulated, which contributes to their physiologic function. PECAM-1 (CD31) is an inhibitory receptor that facilitates TGF-β-mediated suppression of T cell activity. It is well established in CD4 T cells that PECAM-1 is expressed in naïve recent thymic emigrants, but is down-regulated after acute T cell activation and absent from memory cells. The extent to which PECAM-1 expression is similarly regulated in CD8 T cells is much less well characterized. We evaluated T cells recovered from mice after infection with a model intracellular pathogen and determined that, in CD8 T cells, PECAM-1 expression was strongly down-regulated during acute infection but re-expressed to intermediate levels in memory cells. Down-regulation of PECAM-1 expression in CD8 T cells was transcriptionally regulated and affected by the strength and nature of TCR signaling. PECAM-1 was also detected on the surface of human activated/memory CD8 , but not CD4 T cells. These data demonstrate that PECAM-1 expression is dynamically regulated, albeit differently, in both CD4 and CD8 T cells. Furthermore, unlike memory CD4 T cells, memory CD8 T cells retain PECAM-1 expression and have the potential to be modulated by this inhibitory receptor.

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Developmentally determined reduction in CD31 during gestation is associated with CD8 + T cell effector differentiation in preterm infants

Cited by 23 publications

References 37 publications

Dissecting the defects in the neonatal CD8+ T-cell response

Dissecting the defects in the neonatal CD8+ T-cell response

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

Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8+ T cells

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