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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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
Author(s)
Silva J.G., Pais Ferreira D., Dumez A., Wyss T., Veber R., Danilo M., Pinschewer D.D., Charmoy M., Held W.
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
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
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