圣犹达儿童研究医院Ben Youngblood研究小组报道，在SCID-X1基因治疗后，人体内迅速出现先天样记忆T细胞。相关论文发表在2025年7月31日出版的《免疫学》杂志上。

研究人员描述了虚拟记忆T细胞在早期人类生活中的起源。一项对婴儿X连锁严重联合免疫缺陷（SCID-X1）基因治疗后外周T细胞的纵向分析显示，先天样记忆CD8⁺ T细胞早期富集，表达NKG2A、先天相关转录谱和独特的T细胞受体（TCR）库。从头开始的先天样记忆NKG2A⁺ T细胞亚群的全基因组DNA甲基化分析证实了一个亚群特异性的表观遗传特征，包括一个平衡的效应反应。

此外，在体外用IL-12和IL-18刺激NKG2A⁺ T细胞可导致抗原非依赖性干扰素γ (IFNγ)的表达。总的来说，这些数据表明，NKG2A⁺先天样记忆T细胞在人类生命早期发育，并在表观遗传学上准备以抗原独立的方式快速引发效应细胞因子。

研究人员表示，虚拟记忆T细胞具有先天免疫细胞的特征，代表了先天免疫和适应性免疫之间的发育连续体。

附：英文原文

Title: Innate-like memory T cells rapidly emerge in humans after gene therapy for SCID-X1 test

Author: Anoop Babu Vasandan, Hossam A. Abdelsamed, Shannon K. Boi, Grace Ward, Shanta Alli, Tian Mi, Xin Lan, Xusheng Zhang, Morton J. Cowan, Jennifer M. Puck, Aleksandra Petrovic, David Rawlings, Albert Zhou, Ewelina Mamcarz, Stephen Gottschalk, Caitlin C. Zebley, Ben Youngblood

Issue&Volume: 2025-07-31

Abstract: Virtual memory T cells, possessing features of innate immune cells, represent a developmental continuum between innate and adaptive immunity. Here, we describe the genesis of virtual memory T cells during early human life. A longitudinal analysis of peripheral T cells after gene therapy for X-linked severe combined immunodeficiency (SCID-X1) in infants revealed an early enrichment of innate-like memory CD8+ T cells that expressed NKG2A, innate-associated transcriptional profiles, and a distinct T cell receptor (TCR) repertoire. Genome-wide DNA methylation profiling of the de novo innate-like memory NKG2A+ T cell subset confirmed a subset-specific epigenetic signature that included a poised effector response. Furthermore, ex vivo stimulation of NKG2A+ T cells with IL-12 and IL-18 resulted in antigen-independent interferon gamma (IFNγ) expression. Collectively, these data indicate that NKG2A+ innate-like memory T cells develop early in human life and are epigenetically poised to rapidly elicit effector cytokines in an antigen-independent manner.

DOI: 10.1016/j.immuni.2025.07.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00311-5