Few studies have investigated immune cell ontogeny throughout the neonatal and early paediatric period, where there is often increased vulnerability to infections. Here, we evaluated the dynamics of two critical T cell populations, regulatory (Treg) cells and Th17 cells, over the first 36 weeks of life. Firstly, we observed distinct CD4⁺ T cells phenotypes between cord blood and peripheral blood, collected within 12 hours of birth, showing that cord blood is not a surrogate for newborn blood. Secondly, both Treg and Th17 cells expanded in a synchronous fashion over 36 weeks of life. However, comparing infants exposed to HIV in utero, but remaining uninfected (iHEU), with HIV-unexposed uninfected control infants (iHUU), there was a lower frequency of peripheral blood Treg cells at birth, resulting in a delayed expansion, and then declining again at 36 weeks. Focusing on birth events, we found that Treg cells co-expressing CCR4 and α4β7 inversely correlated with plasma concentrations of CCL17 (the ligand for CCR4) and intestinal fatty acid binding protein (iFABP), IL-7 and CCL20. This was in contrast to Th17 cells, which showed a positive association with these plasma analytes. Thus, despite the stereotypic expansion of both cell subsets over the first few months of life, there was a disruption in the balance of Th17 to Treg cells at birth likely being a result of gut damage and homing of newborn Treg cells from the blood circulation to the gut.

中文翻译：

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HIV 暴露和肠道上皮损伤破坏了婴儿期 Tregulatory 和 Th17 细胞的刻板扩张

很少有研究调查整个新生儿期和儿科早期的免疫细胞个体发育，在这些时期，感染的脆弱性通常会增加。在这里，我们评估了两个关键 T 细胞群、调节性 (Treg) 细胞和 Th17 细胞在生命的前 36 周内的动态。首先，我们在出生 12 小时内收集的脐带血和外周血之间观察到不同的 CD4 ⁺ T 细胞表型，表明脐带血不是新生儿血的替代品。其次，Treg 和 Th17 细胞在 36 周的生命中以同步方式扩增。然而，比较子宫内暴露于 HIV 的婴儿，但保持未感染 (iHEU)，对于未暴露于 HIV 的未感染对照婴儿 (iHUU)，出生时外周血 Treg 细胞的频率较低，导致扩增延迟，然后在 36 周时再次下降。关注出生事件，我们发现共表达 CCR4 和 α4β7 的 Treg 细胞与 CCL17（CCR4 的配体）和肠道脂肪酸结合蛋白 (iFABP)、IL-7 和 CCL20 的血浆浓度呈负相关。这与 Th17 细胞形成对比，后者与这些血浆分析物呈正相关。因此，尽管在生命的最初几个月内两种细胞亚群都出现了刻板扩张，但出生时 Th17 与 Treg 细胞的平衡被破坏，这可能是由于肠道损伤和新生 Treg 细胞从血液循环中归巢到肠道。