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Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans

Galletti, Giovanni, Simone, Gabriele De, Mazza, Emilia M.C., Puccio, Simone, Mezzanotte, Claudia, Bi, Timothy M., Davydov, Alexey N., Metsger, Maria, Scamardella, Eloise, Alvisi, Giorgia, Paoli, Federica De, Zanon, Veronica, Scarpa, Alice, Mavilio, Barbara, Gattinoni, Luca, Boi, Shannon K., Youngblood, Benjamin A., Jones, Rhiannon E., Baird, Duncan, Gostick, Emma, Llewellyn-Lacey, Sian, Ladell, Kristin, Price, David A., Chudakov, Dmitriy M., Newell, Evan W., Casucci, Monica and Lugli, Enrico 2020. Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans. Nature Immunology 10.1038/s41590-020-0791-5
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T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of First Compliant Deposit: 18 September 2020
Date of Acceptance: 14 August 2020
Last Modified: 29 Oct 2020 12:15

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