Replicative history marks transcriptional and functional disparity in the CD8 + T cell memory pool

Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8 memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that rep...

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Published in:Nature immunology Vol. 23; no. 5; pp. 791 - 801
Main Authors: Bresser, Kaspar, Kok, Lianne, Swain, Arpit C, King, Lisa A, Jacobs, Laura, Weber, Tom S, Perié, Leïla, Duffy, Ken R, de Boer, Rob J, Scheeren, Ferenc A, Schumacher, Ton N
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.05.2022
Subjects:
CD8 antigen
CD8-Positive T-Lymphocytes
Immune clearance
Immune response
Immunologic Memory
Immunological memory
Lymphocytes
Lymphocytes T
Memory cells
Pathogens
Stem cells
Transcriptomics
ISSN:1529-2908, 1529-2916, 1529-2916
Online Access:Get full text
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Summary:Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8 memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically 'record' the replicative history of different CD8 T cell populations throughout a pathogen-specific immune response, we demonstrate that the central memory T (T ) cell pool is marked by a higher number of prior divisions than the effector memory T cell pool, owing to the combination of strong proliferative activity during the acute immune response and selective proliferative activity after pathogen clearance. Furthermore, by combining DivisionRecorder analysis with single-cell transcriptomics and functional experiments, we show that replicative history identifies distinct cell pools within the T compartment. Specifically, we demonstrate that lowly divided T cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation. These data provide the first evidence that a stem-cell-like memory T cell pool that reconstitutes the CD8 T cell effector pool upon reinfection is marked by prior quiescence.
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ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-022-01171-9