Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
Galletti G, De Simone G, Mazza EMC, Puccio S, Mezzanotte C, Bi TM, Davydov AN, Metsger M, Scamardella E, Alvisi G, De Paoli F, Zanon V, Scarpa A, Camisa B, Colombo FS, Anselmo A, Peano C, Polletti S, Mavilio D, Gattinoni L, Boi SK, Youngblood BA, Jones RE, Baird DM, Gostick E, Llewellyn-Lacey S, Ladell K, Price DA, Chudakov DM, Newell EW, Casucci M, Lugli E (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 21
Pages Range: 1552-1562
Journal Issue: 12
DOI: 10.1038/s41590-020-0791-5
Abstract
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.
Involved external institutions
Istituto di ricovero e cura a carattere scientifico (IRCCS)
Italy (IT)
Università Vita-Salute San Raffaele (UniSR)
Italy (IT)
Fred Hutchinson Cancer Research Center
United States (USA) (US)
Central European Institute of Technology (CEITEC)
Czech Republic (CZ)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Istituto Clinico Humanitas
Italy (IT)
National Cancer Institute (NCI)
United States (USA) (US)
St. Jude Children’s Research Hospital
United States (USA) (US)
Cardiff University
United Kingdom (GB)
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Russian Federation (RU)
Italy (IT)
Università Vita-Salute San Raffaele (UniSR)
Italy (IT)
Fred Hutchinson Cancer Research Center
United States (USA) (US)
Central European Institute of Technology (CEITEC)
Czech Republic (CZ)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Istituto Clinico Humanitas
Italy (IT)
National Cancer Institute (NCI)
United States (USA) (US)
St. Jude Children’s Research Hospital
United States (USA) (US)
Cardiff University
United Kingdom (GB)
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Russian Federation (RU)
How to cite
APA:
Galletti, G., De Simone, G., Mazza, E.M.C., Puccio, S., Mezzanotte, C., Bi, T.M.,... Lugli, E. (2020). Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans. Nature Immunology, 21(12), 1552-1562. https://doi.org/10.1038/s41590-020-0791-5
MLA:
Galletti, Giovanni, et al. "Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans." Nature Immunology 21.12 (2020): 1552-1562.
BibTeX: Download