Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans [Bulk RNA-seq]

The development of human adaptive immunity progresses faster than previously appreciated, with the emergence of memory CD4+ T cells alongside regulatory T (Treg) cells by the second trimester of pregnancy. We previously identified a prenatal-specific subset of PLZF+ CD4+ T cells with heightened effector potential that accounted for most memory T cells in the developing intestine and accumulated in the cord blood of infants exposed to prenatal inflammatory pathologies. However, the signals that drive their tissue distribution and effector maturation are unknown. Here, we define the transcriptional and functional heterogeneity of prenatal PLZF+ CD4+ T cells and identify compartmentalization of Th-like effector function across the small intestine (SI) and mesenteric lymph nodes (MLN). Prenatal intestine PLZF+CD4+ T cells were isolated by Fluorescence-activated cell sorting (FACS) using proxy markers were stimulated by PMA/ionomycin and processed for bulk RNAseq.

人类适应性免疫的发育进程远超此前认知，妊娠中期即可同时出现记忆性CD4+ T细胞与调节性T（Treg）细胞。我们此前曾鉴定出一类产前特异性的PLZF+ CD4+ T细胞亚群，该亚群具备较强的效应潜能，是发育中肠道内绝大多数记忆性T细胞的来源，且在暴露于产前炎症性病变的婴儿脐带血中显著富集。然而，调控这类细胞组织分布与效应成熟的信号机制至今仍不明晰。本研究阐明了产前PLZF+ CD4+ T细胞的转录与功能异质性，并揭示了小肠（SI）与肠系膜淋巴结（MLN）中类辅助性T细胞（Th）样效应功能的区域化分布特征。本研究通过荧光激活细胞分选（Fluorescence-activated cell sorting, FACS）借助替代标志物分离得到产前肠道PLZF+ CD4+ T细胞，经佛波酯/离子霉素刺激后开展批量RNA测序（bulk RNAseq）分析。