A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool

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,...

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Published in:The Journal of experimental medicine Vol. 217; no. 10
Main Authors: Kok, Lianne, Dijkgraaf, Feline E, Urbanus, Jos, Bresser, Kaspar, Vredevoogd, David W, Cardoso, Rebeca F, Perié, Leïla, Beltman, Joost B, Schumacher, Ton N
Format: Journal Article
Language:English
Published: United States 05.10.2020
Subjects:
Animals
CD8-Positive T-Lymphocytes - immunology
Cell Lineage
Gene Expression Profiling
Immunologic Memory
Mice
Mice, Inbred C57BL
Precursor Cells, T-Lymphoid - immunology
ISSN:1540-9538, 1540-9538
Online Access:Get more information
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Summary: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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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20191711