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Central memory CD8 + T cells derive from stem-like Tcf7 hi effector cells in the absence of cytotoxic differentiation

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2020-11, Vol.53 (5), p.985
Main Authors: Pais Ferreira, Daniela, Silva, Joana Gomes, Wyss, Tania, Fuertes Marraco, Silvia A, Scarpellino, Léonardo, Charmoy, Mélanie, Maas, Roeltje, Siddiqui, Imran, Tang, Li, Joyce, Johanna A, Delorenzi, Mauro, Luther, Sanjiv A, Speiser, Daniel E, Held, Werner
Format: Article
Language:English
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Summary: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 Tcf7 cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically, Tcf1 counteracted the differentiation of Tcf7 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.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2020.09.005