Epstein-Barr virus infection induces tissue-resident memory T cells in mucosal lymphoid tissues.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL JCI insight Pub Date : 2024-10-22 DOI:10.1172/jci.insight.173489
Daniel Kirchmeier, Yun Deng, Lisa Rieble, Michelle Böni, Fabienne Läderach, Patrick Schuhmachers, Alma Delia Valencia-Camargo, Anita Murer, Nicole Caduff, Bithi Chatterjee, Obinna Chijioke, Kyra Zens, Christian Münz
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Abstract

EBV contributes to around 2% of all tumors worldwide. Simultaneously, more than 90% of healthy human adults persistently carry EBV without clinical symptoms. In most EBV carriers, it is thought that virus-induced tumorigenesis is prevented by cell-mediated immunity. Specifically, memory CD8+ T cells recognize EBV-infected cells during latent and lytic infection. Using a symptomatic primary infection model, similar to infectious mononucleosis (IM), we found EBV-induced CD8+ tissue resident memory T cells (TRMs) in mice with a humanized immune system. These human TRMs were preferentially established after intranasal EBV infection in nasal-associated lymphoid tissues (NALT), equivalent to tonsils, the primary site of EBV infection in humans. They expressed canonical TRM markers, including CD69, CD103, and BLIMP-1, as well as granzyme B, CD107a, and CCL5. Despite cytotoxic activity and cytokine production ex vivo, these TRMs demonstrated reduced CD27 expression and proliferation and failed to control EBV viral loads in the NALT during infection, although effector memory T cells (TEMs) controlled viral titers in spleen and blood. Overall, TRMs are established in mucosal lymphoid tissues by EBV infection, but primarily, systemic CD8+ T cell expansion seems to control viral loads in the context of IM-like infection.

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Epstein Barr 病毒感染会诱导粘膜淋巴组织中的组织驻留记忆 T 细胞。
全球约有 2% 的肿瘤是由 Epstein Barr 病毒(EBV)引起的。同时,超过 90% 的健康成年人持续携带 EBV,但没有临床症状。在大多数 EBV 携带者中,人们认为病毒诱导的肿瘤发生是由细胞介导的免疫所阻止的。具体来说,记忆性 CD8+ T 细胞能在潜伏感染和溶解感染期间识别 EBV 感染细胞。通过使用类似于传染性单核细胞增多症(IM)的无症状原发感染模型,我们在具有人源化免疫系统的小鼠体内发现了 EBV 诱导的 CD8+ 组织驻留记忆 T 细胞(TRMs)。鼻腔相关淋巴组织(NALT)相当于扁桃体,是人类感染 EBV 的主要部位。它们表达典型的 TRM 标记,包括 CD69、CD103 和 BLIMP-1,以及 Granzyme B、CD107a 和 CCL5。尽管这些TRMs在体外具有细胞毒性活性并能产生细胞因子,但它们的CD27表达和增殖能力都有所下降,在感染期间也未能控制NALT中的EBV病毒载量,尽管效应记忆T细胞(TEMs)能控制脾脏和血液中的病毒滴度。总之,EBV 感染会在粘膜淋巴组织中建立 TRMs,但在类似 IM 感染的情况下,似乎主要是全身 CD8+ T 细胞扩增能控制病毒载量。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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