Differential expansion of T central memory precursor and effector subsets is regulated by division speed

Lorenz Kretschmer, Michael Flossdorf, Jonas Mir, Yi-Li Cho, Marten Plambeck, Irina Treise, Albulena Toska, Susanne Heinzel, Matthias Schiemann, Dirk H. Busch () and Veit R. Buchholz ()
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Lorenz Kretschmer: Technische Universität München (TUM)
Michael Flossdorf: Technische Universität München (TUM)
Jonas Mir: Technische Universität München (TUM)
Yi-Li Cho: Technische Universität München (TUM)
Marten Plambeck: Technische Universität München (TUM)
Irina Treise: Technische Universität München (TUM)
Albulena Toska: Technische Universität München (TUM)
Susanne Heinzel: The Walter and Eliza Hall Institute of Medical Research
Matthias Schiemann: Technische Universität München (TUM)
Dirk H. Busch: Technische Universität München (TUM)
Veit R. Buchholz: Technische Universität München (TUM)

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract While antigen-primed T cells proliferate at speeds close to the physiologic maximum of mammalian cells, T cell memory is maintained in the absence of antigen by rare cell divisions. The transition between these distinct proliferative programs has been difficult to resolve via population-based analyses. Here, we computationally reconstruct the proliferative history of single CD8+ T cells upon vaccination and measure the division speed of emerging T cell subsets in vivo. We find that slower cycling central memory precursors, characterized by an elongated G1 phase, segregate early from the bulk of rapidly dividing effector subsets, and further slow-down their cell cycle upon premature removal of antigenic stimuli. In contrast, curtailed availability of inflammatory stimuli selectively restrains effector T cell proliferation due to reduced receptivity for interleukin-2. In line with these findings, persistence of antigenic but not inflammatory stimuli throughout clonal expansion critically determines the later size of the memory compartment.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13788-w

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DOI: 10.1038/s41467-019-13788-w

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