埃默里大学医学院Jacob E. Kohlmeier小组在研究中取得进展。他们的研究显示，人肺CD8⁺组织驻留记忆T细胞衍生的干扰素-γ在气道上皮细胞中协调亚群特异性抗病毒编程。这一研究成果发表在2025年11月26日出版的国际学术期刊《免疫学》上。

课题组人员检测了人肺CD8⁺ T细胞的表型特征和效应功能，这些细胞特异性针对其流行的人类病毒主题——流感病毒、呼吸道合胞病毒（RSV）、巨细胞病毒（CMV）和EB病毒（EBV）。病毒特异性肺CD8⁺ T细胞表现出基于病毒趋向性的不同组织驻留记忆（Trm）表型，但共享核心转录和效应程序。同源抗原刺激肺Trm细胞触发干扰素-γ (IFNγ)介导的肺先天免疫细胞和气道上皮细胞激活程序。基底上皮细胞对IFNγ最敏感，在CD8⁺ Trm细胞激活后，基底上皮细胞和分泌上皮细胞亚群中IFN刺激基因通路的表达存在差异。在模拟肺部流感感染的气液界面培养中，快速的IFNγ信号传导是激活分层上皮中的抗病毒途径并保护其免受感染的必要和充分条件。因此，肺Trm细胞通过快速IFNγ驱动的上皮编程来协调早期粘膜防御，以限制人类呼吸道病毒的传播。

据悉，肺驻留CD8⁺ T细胞位于病毒进入和复制的初始位置。

附：英文原文

Title: Human lung CD8+ tissue-resident memory T cell-derived interferon-γ orchestrates subset-specific antiviral programming in airway epithelial cells

Author: Cameron L.R. Mattingly, Ariana R. Jimenez, M. Elliott Williams, Kirsten N. Kost, Laurel A. Lawrence, Thien Duy Chen, Sarah E. Michalets, Jenna L. Lobby, Yixel Soto-Vázquez, Kathryn M. Moore, Sakeenah L. Hicks, Shamika Danzy, Jennifer L. Elliott, Christopher D. Scharer, Alison Swaims-Kohlmeier, Anice C. Lowen, Aneesh Mehta, Jacob E. Kohlmeier

Issue&Volume: 2025-11-26

Abstract: Lung resident CD8+ T cells are situated at the site of initial viral entry and replication. Here, we examined the phenotypic profiles and effector functions of human lung CD8+ T cells specific for four prevalent human viruses—influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Virus-specific lung CD8+ T cells exhibited distinct tissue-resident memory (Trm) phenotypes based on viral tropism yet shared core transcriptional and effector programs. Cognate antigen stimulation of lung Trm cells triggered interferon-γ (IFNγ)-mediated activation programs in lung innate immune and airway epithelial cells. Basal epithelial cells were most responsive to IFNγ, with differential expression of IFN-stimulated gene pathways in basal and secretory epithelial cell subsets following CD8+ Trm cell activation. In air-liquid interface cultures modeling influenza infection of the lung, rapid IFNγ signaling was necessary and sufficient to activate antiviral pathways in stratified epithelium and protect against infection. Thus, lung Trm cells coordinate early mucosal defense through rapid IFNγ-driven epithelial programming to restrict respiratory virus propagation in humans.

DOI: 10.1016/j.immuni.2025.11.003

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00505-9