A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool.
A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool.
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DOI：
10.1084/jem.20191711
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
Schumacher TN
中科院分区：
文献类型：
--
作者：
Kok L;Dijkgraaf FE;Urbanus J;Bresser K;Vredevoogd DW;Cardoso RF;Perié L;Beltman JB;Schumacher TN
局部炎症后，CD8+ T 细胞发育成组织驻留记忆 T 细胞 (TRM)。通过结合谱系追踪和单细胞转录组分析，作者表明循环 T 细胞池中含有 TRM 前体，这些前体在进入组织之前就决定了 TRM 的命运。越来越多的证据强调组织驻留记忆 T 细胞 (TRM) 在防御复发病原体和恶性肿瘤中的作用。然而，人们对这些细胞的起源及其与其他 CD8+ T 细胞区室的亲缘关系知之甚少。为了解决这个问题，我们通过谱系追踪和单细胞转录组分析，追踪单个初始 CD8+ T 细胞的抗原特异性后代到 T 效应子 (TEFF)、T 循环记忆 (TCIRCM) 和 TRM 池。我们证明，T 细胞克隆的一个子集具有形成 TRM 的增强能力，并且 TRM 命运相关基因的富集表达在此类克隆的循环 TEFF 后代中已经很明显。此外，我们还证明，在进入皮肤之前，产生 TRM 的能力在克隆水平上永久印记。总的来说，这些数据为早期 TRM 命运决定以及循环 TEFF 室中定向 TRM 前体细胞的存在提供了令人信服的证据。
Following local inflammation, CD8+ T cells develop into tissue-resident memory T cells (TRM). Through combined lineage tracing and single-cell transcriptome analysis, the authors show that the circulating T cell pool harbors TRM precursors that commit to the TRM fate before tissue entry. An increasing body of evidence emphasizes the role of tissue-resident memory T cells (TRM) in the defense against recurring pathogens and malignant neoplasms. However, little is known with regard to the origin of these cells and their kinship to other CD8+ T cell compartments. To address this issue, we followed the antigen-specific progeny of individual naive CD8+ T cells to the T effector (TEFF), T circulating memory (TCIRCM), and TRM pools by lineage-tracing and single-cell transcriptome analysis. We demonstrate that a subset of T cell clones possesses a heightened capacity to form TRM, and that enriched expression of TRM–fate-associated genes is already apparent in the circulating TEFF offspring of such clones. In addition, we demonstrate that the capacity to generate TRM is permanently imprinted at the clonal level, before skin entry. Collectively, these data provide compelling evidence for early stage TRM fate decisions and the existence of committed TRM precursor cells in the circulatory TEFF compartment.
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影响因子：
32.4
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Herndler-Brandstetter D;Ishigame H;Shinnakasu R;Plajer V;Stecher C;Zhao J;Lietzenmayer M;Kroehling L;Takumi A;Kometani K;Inoue T;Kluger Y;Kaech SM;Kurosaki T;Okada T;Flavell RA
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64.8
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影响因子：
32.4
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通讯作者：
von Andrian, Ulrich H.