中山大学何晓顺小组的研究显示，全身免疫活动发生在人体免疫系统成熟的过程中。相关论文于2025年10月28日发表在《细胞》杂志上。
利用单细胞RNA测序和T细胞受体测序，研究人员分析了来自23个器官的321个样本的2868420个免疫细胞，包括成人组织作为比较物。该课题组人员发现胸腺外CD4+ T细胞亚群介导TOX2+前体细胞向成熟幼稚CD4+ T细胞的转变。与流行的胎儿免疫静止模式相反，课题组人员发现广泛的记忆/活化T细胞和组织驻留记忆克隆在各个器官中共享，表明全身免疫活动超越了局部屏障防御。细胞间通讯和功能分析表明抑制胎儿T细胞活化的两种耐受机制：ARG1+中性粒细胞和PTGES3/PTGER4信号通路。该课题组人员还发现造血干细胞（HSCs）分散在多个器官，并表明来自非典型造血器官的HSCs分化成不同的免疫谱系。这些发现为胎儿和成人的免疫系统成熟和耐受性提供了见解。
研究人员表示，妊娠中期是人体免疫系统发育的关键阶段。
附：英文原文
Title: Systemic immune activity occurs during human immune system maturation
Author: Shuai He, Chun-Ling Luo, Tao Luo, Hai-Tian Chen, Shao-Feng Zhang, Jia-Xin Jiang, Xiao-Yi Wang, Dong Ma, Shuang-Lian Zhao, An-Yi Xu, Jing-Jing He, Zhao-Hui Ruan, Wen-Xin Yan, Zi-Hao Xu, Yang Liu, Qi-Tao Huang, Yu-Jie Gan, Tie-Long Wang, Yun-Hua Tang, Xiao-Rui Liu, Cai-Xia Zhu, Liang Li, Zi-Lian Wang, Zhi-Yong Guo, Jin-Xin Bei, Xiao-Shun He
Issue&Volume: 2025-10-28
Abstract: The second trimester of pregnancy is a pivotal stage in human immune system development. Utilizing single-cell RNA sequencing and T cell receptor sequencing, we profiled 2,868,420 immune cells from 321 samples across 23 organs, including adult tissues as comparators. We identify an extrathymic CD4+ T cell subset mediating TOX2+ precursor cells’ transition to mature naive CD4+ T cells. Contrary to the prevailing paradigm of fetal immune quiescence, we uncover widespread memory/activated T cells and tissue-resident memory clones shared across organs, indicating systemic immune activity beyond localized barrier defense. Cell-cell communication and functional assays indicate two tolerance mechanisms that suppress fetal T cell activation: ARG1+ neutrophils and a PTGES3/PTGER4 signaling pathway. We also find that hematopoietic stem cells (HSCs) disperse across multiple organs and show that HSCs from non-canonical hematopoietic organs differentiate into diverse immune lineages. These findings provide insights into human immune system maturation and tolerance in fetuses and adults.
DOI: 10.1016/j.cell.2025.10.003
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01132-8