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Extremely Preterm Infants Have Significant Alterations in Their Conventional T Cell Compartment during the First Weeks of Life
The Journal of Immunology ( IF 3.6 ) Pub Date : 2019-12-04 , DOI: 10.4049/jimmunol.1900941
Khaleda Rahman Qazi 1 , Georg Bach Jensen 2, 3 , Marieke van der Heiden 4 , Sophia Björkander 4 , Ulrika Holmlund 4 , Yeneneh Haileselassie 4 , Efthymia Kokkinou 4 , Giovanna Marchini 5 , Maria C Jenmalm 2 , Thomas Abrahamsson 2, 3 , Eva Sverremark-Ekström 4
Affiliation  

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. 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.

中文翻译:

极早产儿在出生后最初几周的常规 T 细胞室有显着变化

要点 ELGAN/ELBW 新生儿淋巴细胞减少,其 T 细胞的归巢能力发生改变。患有绒毛膜羊膜炎的 ELGAN/ELBW 婴儿的 Treg 群体发生了改变。极早产儿特别容易受到感染,这可能是因为免疫功能严重受损。然而,人们对这一弱势群体生命早期 T 细胞区室的组成知之甚少。我们对参与益生菌随机安慰剂对照研究的极低出生体重 (ELBW; <1000 g) 的人类极低胎龄新生儿 (ELGAN) 的外周常规 T 细胞室进行了全面的基于表型流式细胞术的纵向分析。补充。在第 14 天、第 28 天和经后第 36 周收集来自 ELGAN/ELBW 新生儿的 PBMC。对足月 14 岁的新生儿进行了比较。早产儿的总 CD4+ 和 CD8+ T 细胞频率明显较低。CD8+ 人群中的减少更为明显,导致 CD4/CD8 比率增加。早产儿也比足月儿更偏向于 Th2。尽管 ELGAN/ELBW 早产新生儿中调节性 T 细胞的频率似乎正常,但它们的归巢受体 α4β7、CCR4 和 CCR9 的表达发生了改变。值得注意的是,在第 14 天之前发展为坏死性小肠结肠炎的 ELGAN/ELBW 婴儿在第 14 天的 CD4+T 细胞中具有更高的 CCR9 表达。绒毛膜羊膜炎与早产组中 T 调节细胞频率和功能特征的降低明显相关。最后,益生菌补充剂罗伊氏乳杆菌不会对传统 T 细胞区室造成任何表型变化。总之,ELGAN/ELBW 新生儿中 T 细胞区室的显着不成熟可能至少部分解释了他们对严重免疫介导的疾病的易感性增加。
更新日期:2019-12-04
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