Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands.
Institut Curie, Université Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR168, Paris, France.
J Exp Med. 2020 Oct 5;217(10). doi: 10.1084/jem.20191711.
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.
越来越多的证据强调了组织驻留记忆 T 细胞 (TRM) 在抵御反复出现的病原体和恶性肿瘤中的作用。然而，人们对于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，跟踪了单个幼稚 CD8+T 细胞的抗原特异性后代在 T 效应 (TEFF)、T 循环记忆 (TCIRCM) 和 TRM 池中的情况。我们证明，一部分 T 细胞克隆具有形成 TRM 的更高能力，并且在这种克隆的循环 TEFF 后代中，已经明显富集了与 TRM 命运相关的基因表达。此外，我们证明，在进入皮肤之前，在克隆水平上就已经永久地烙印了生成 TRM 的能力。总的来说，这些数据为早期 TRM 命运决定以及循环 TEFF 区室中存在定型的 TRM 前体细胞提供了有力的证据。
