Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-06-07 DOI:10.1126/sciimmunol.adk8141

Taylor A. Heim, Austin C. Schultz, Ines Delclaux, Vanessa Cristaldi, Madeline J. Churchill, Katherine S. Ventre, Amanda W. Lund

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Abstract

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T_RMs) play an important role in site-specific immune memory, yet how LN T_RMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8⁺ T cells as they seeded skin and LN T_RMs using a model of vaccinia virus–induced skin infection. LN T_RMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8⁺ T cells from the skin, already poised for residence. Effector CD8⁺ T cell transit through skin was required to populate LN T_RMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T_RMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8⁺ T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.

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淋巴管转运为皮肤引流淋巴结中的细胞毒性常驻记忆 T 细胞播下了种子。

淋巴运输塑造了淋巴结（LN）的同种免疫复合物。淋巴结驻留的记忆 T 细胞（TRMs）在特定部位的免疫记忆中发挥着重要作用，但淋巴结 TRMs 在病毒感染后如何重新形成仍不清楚。在这里，我们利用疫苗病毒诱导的皮肤感染模型追踪了抗病毒 CD8+ T 细胞在皮肤和 LN TRMs 上播种时的解剖分布。LN TRMs定位于受感染皮肤的引流LNs（dLNs），它们的形成依赖于效应CD8+ T细胞从皮肤的淋巴排出，而效应CD8+ T细胞已经做好了定居的准备。效应CD8+ T细胞穿过皮肤是在dLNs中形成LN TRMs的必要条件，皮肤中的抗原相遇强化了这一过程。此外，在没有循环记忆 T 细胞的情况下，LN TRMs 对病毒再侵具有保护作用。这些数据表明，在病毒清除过程中，组织浸润的 CD8+ T 细胞亚群从组织中排出，并在 dLN 盆地建立了一层区域保护。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.