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Published on: December 7, 2015
Extremely Preterm Infants Have Significant Alterations in Their Conventional T Cell Compartment during the First
Khaleda Rahman Qazi1, Georg Bach Jensen2,3, Marieke van der Heiden4
1Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden; qazi.khaleda.rahman@su.se.
Insights
Extremely preterm infants show immature T cell compartments, impacting their infection susceptibility. Probiotic supplementation did not alter these T cell patterns in extremely low gestational age neonates.
Area of Science:
- Neonatal Immunology
- T cell biology
- Preterm infant health
Background:
- Extremely preterm neonates exhibit heightened infection susceptibility due to underdeveloped immune systems.
- The T cell compartment's early-life composition in this vulnerable group remains poorly understood.
- Understanding these immune deficits is crucial for improving preterm infant outcomes.
Purpose of the Study:
- To longitudinally analyze the peripheral conventional T cell compartment in extremely low gestational age neonates (ELGAN) with extremely low birth weight (ELBW).
- To compare T cell composition in ELGAN/ELBW neonates with full-term neonates.
- To investigate the impact of probiotic supplementation and factors like chorioamnionitis on T cell phenotypes.
Main Methods:
- Longitudinal flow cytometry analysis of peripheral T cells (CD4+, CD8+, regulatory T cells) in ELGAN/ELBW neonates at multiple time points.
- Comparison with T cell profiles of full-term neonates.
- Assessment of homing receptor expression (α4β7, CCR4, CCR9) and correlation with clinical outcomes (necrotizing enterocolitis, chorioamnionitis).
Main Results:
- ELGAN/ELBW neonates displayed significantly lower total CD4+ and CD8+ T cell frequencies, with a higher CD4/CD8 ratio.
- Preterm infants showed a Th2-skewed immune profile compared to full-term infants.
- Regulatory T cells in preterm infants had altered homing receptor expression; chorioamnionitis was linked to reduced regulatory T cell frequency and function.
- Necrotizing enterocolitis was associated with increased CCR9 expression on CD4+ T cells.
- Probiotic supplementation with *Lactobacillus reuteri* did not alter the conventional T cell compartment phenotype.
Conclusions:
- Significant T cell compartment immaturities are present in ELGAN/ELBW neonates.
- These immune deficits may contribute to the increased susceptibility to severe immune-mediated morbidities in preterm infants.
- Further research into immune modulation strategies for preterm infants is warranted.
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 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.
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