Govindaraj Dhanapal, Jensen Georg Bach, Rahman Qazi Khaleda, Sverremark-Ekström Eva, Abrahamsson Thomas, Jenmalm Maria C
Division of Inflammation and Infection (II), Department of Biomedical and Clinical Sciences (BKV) Linköping University Linköping Sweden.
Crown Princess Victoria Children's Hospital Linköping County of Östergötland Sweden.
Clin Transl Immunology. 2024 May 10;13(5):e1510. doi: 10.1002/cti2.1510. eCollection 2024.
Extremely preterm (EPT; gestational week < 28 + 0, < 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants.
Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads.
The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-γ, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses.
Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.
极早产儿（EPT；孕周<28+0，体重<1000g）易受感染和坏死性小肠结肠炎影响，这些是导致死亡率和发病率的重要因素。然而，关于其免疫成熟的知识仍然有限。我们在此研究了EPT婴儿功能性T细胞能力的纵向发育情况。
从参与DSM 17938益生菌补充剂随机、双盲、安慰剂对照研究的EPT婴儿中，在第14天和第28天以及孕36+0周（Gw36）分离外周血单个核细胞。从25名足月（FT）婴儿第14天采集的血液用作对照。用人T细胞激活剂CD3/CD28磁珠刺激后，通过综合Luminex检测板测定免疫介质的分泌情况。
EPT婴儿在第14天时许多介质水平较低，而EPT婴儿中几种趋化因子的分泌高于FT婴儿。此外，EPT婴儿中Th2:Th1细胞因子比值高于FT婴儿。从第14天到第28天，然后在Gw36时，观察到EPT婴儿中例如IFN-γ、TNF和IL-17A的分泌逐渐升高。在第28天时观察到许多促炎介质水平升高。益生菌补充或围产期因素（如临床绒毛膜羊膜炎、先兆子痫和分娩方式）不影响细胞因子和趋化因子反应。
与FT婴儿相比，EPT婴儿中T细胞激活诱导的免疫介质在第14天时主要减少且Th2偏向，但在Gw36时大多恢复，表明免疫成熟。第28天时促炎反应增加可能与EPT婴儿中严重免疫相关并发症风险增加有关。
