Emergence and fate of stem cell-like Tcf7<sup>+</sup> CD8<sup>+</sup> T cells during a primary immune response to viral infection.
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Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_0FB9CCAB8627
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Emergence and fate of stem cell-like Tcf7<sup>+</sup> CD8<sup>+</sup> T cells during a primary immune response to viral infection.
Journal
Science immunology
ISSN
2470-9468 (Electronic)
ISSN-L
2470-9468
Publication state
Published
Issued date
17/11/2023
Peer-reviewed
Oui
Volume
8
Number
89
Pages
eadh3113
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
In response to infection, naïve CD8 <sup>+</sup> T (T <sub>N</sub> ) cells yield a large pool of short-lived terminal effector (T <sub>TE</sub> ) cells that eliminate infected host cells. In parallel, a minor population of stem cell-like central memory (T <sub>CM</sub> ) cells forms, which has the capacity to maintain immunity after pathogen clearance. It has remained uncertain whether stem-like T <sub>CM</sub> cells arise by dedifferentiation from a subset of cytolytic T <sub>TE</sub> cells or whether priming generates stem-like cells capable of seeding the T <sub>CM</sub> compartment and, if so, when cytolytic T <sub>TE</sub> cells branch off. Here, we show that CD8 <sup>+</sup> T cells with stem-like properties, which are identified by the expression of TCF1 (encoded by Tcf7), are present across the primary response to infection. Priming programs T <sub>N</sub> cells to undergo multiple cell divisions, over the course of which TCF1 expression is maintained. These TCF1 <sup>+</sup> cells further expand relatively independently of systemic inflammation, antigen dose, or affinity, and they quantitatively yield TCF1 <sup>+</sup> T <sub>CM</sub> cells after pathogen clearance. Inflammatory signals suppress TCF1 expression in early divided TCF1 <sup>+</sup> cells. TCF1 down-regulation is associated with the irreversible loss of self-renewal capacity and the silencing of stem/memory genes, which precedes the stable acquisition of a T <sub>TE</sub> state. TCF1 expression restrains cell cycling, explaining in part the limited expansion of TCF1 <sup>+</sup> relative to TCF1 <sup>-</sup> cells during the primary response. Thus, our data are consistent with terminal differentiation of effector cells being a step-wise process that is initiated by inflammation in primed stem-like cells, which would otherwise become central memory cells by default.
Keywords
Humans, CD8-Positive T-Lymphocytes, Virus Diseases, Stem Cells, Inflammation/metabolism, Immunity
Pubmed
Create date
23/11/2023 14:37
Last modification date
09/12/2023 7:02