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Central memory CD8+ T cells derive from stem-like Tcf7hi effector cells in the absence of cytotoxic differentiation
Abstract
Central memory CD8+ T cells (Tcm) control systemic secondary infections and can protect from chronic infection and cancer as a result of their stem-cell-like capacity to expand, differentiate, and self-renew. Central memory is generally thought to emerge following pathogen clearance and to form based on the de-differentiation of cytolytic effector cells. Here, we uncovered rare effector-phase CD8+ T cells expressing high amounts of the transcription factor Tcf7 (Tcf1) that showed no evidence of prior cytolytic differentiation and that displayed key hallmarks of Tcm cells. These effector-phase Tcf7hi cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically, Tcf1 counteracted the differentiation of Tcf7hi cells and sustained the expression of conserved adult stem-cell genes that were critical for CD8+ T cell stemness. The discovery of stem-cell-like CD8+ T cells during the effector response to acute infection provides an opportunity to optimize Tcm cell formation by vaccination.
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“Reduced PRDM1 expression in the absence of TET2 correlates with hypermethylation within Prdm1 intron 2, which contains a locus that undergoes progressive demethylation during plasma cell differentiation, as well as decreased hydroxymethylation of an intergenic enhancer.”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [173]
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Metadata
- Authors
- Pais Ferreira, D., Silva, J. G., Wyss, T., Fuertes Marraco, S. A., Scarpellino, L., Charmoy, M., Maas, R., Siddiqui, I., Tang, L., Joyce, J. A., Delorenzi, M., Luther, S. A., Speiser, D. E., & Held, W.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 53
- Issue
- 5
- Pages
- 985-1000.e11
- ISSN
- 1074-7613
- Cited by
- 218
- References
- 68
- Language
- en
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- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 381 d)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Krebsliga Schweiz
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