@article{6bed863b35d64c81b48a7dca3277c452,
title = "Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans: Nature Immunology",
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. {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
author = "G. Galletti and {De Simone}, G. and E.M.C. Mazza and S. Puccio and C. Mezzanotte and T.M. Bi and A.N. Davydov and M. Metsger and E. Scamardella and G. Alvisi and {De Paoli}, F. and V. Zanon and A. Scarpa and B. Camisa and F.S. Colombo and A. Anselmo and C. Peano and S. Polletti and D. Mavilio and L. Gattinoni and S.K. Boi and B.A. Youngblood and R.E. Jones and D.M. Baird and E. Gostick and S. Llewellyn-Lacey and K. Ladell and D.A. Price and D.M. Chudakov and E.W. Newell and M. Casucci and E. Lugli",
note = "Cited By :5 Export Date: 11 March 2021 CODEN: NIAMC Correspondence Address: Lugli, E.; Laboratory of Translational Immunology, Italy; email: enrico.lugli@humanitasresearch.it Funding details: 5 ×1000 2019 Funding details: Wellcome Trust, WT Funding details: H2020 European Research Council, ERC;CEI;CER;ERBN, ERC_StG_2014 PERSYST 640511 Funding details: Cancer Research UK, CRUK, C17199/A18246/ A29202 Funding details: European Research Council, ERC, 640511, ERC-2014-STG Funding details: Ministero della Salute, PE-2016-02363915 Funding details: Ministry of Education and Science of the Russian Federation, Minobrnauka, 0908300057056, 82/2015 Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC, IG 20676, IG 21567 Funding details: Central European Institute of Technology, CEITEC, 2020 LQ1601 Funding details: Fondazione Italiana per la Ricerca sul Cancro, FIRC Funding details: Wellcome Trust Centre for Mitochondrial Research, WCMR, 100326/Z/12/Z Funding text 1: The authors thank G. Natoli (European Institute of Oncology, Milan) for assistance with the ATAC-seq protocol, R. Roychoudhuri (University of Cambridge) and M. Iannacone (San Raffaele Scientific Institute, Milan) for critical discussions, and G. Cugini and G. Colombo (Humanitas Clinical and Research Center, Milan) for the provision of lymph node samples. This work was funded by the European Research Council (ERC-2014-STG PERSYST no. 640511 to E.L.) and by the Associazione Italiana per la Ricerca sul Cancro (AIRC IG 20676 to E.L.). Additional support was provided by the Associazione Italiana per la Ricerca sul Cancro (AIRC IG 21567 to D.M.), the Italian Ministry of Health (Bando Ricerca Finalizzata PE-2016-02363915 to D.M.), the Intramural Research Fund of the Humanitas Clinical and Research Center (5 ×1000 2019 Program to D.M.) and Cancer Research UK (C17199/A18246/ A29202 to D.M.B.). G.G., G.D.S., S.P. and E.S. were supported by Fellowships from the Fondazione Italiana per la Ricerca sul Cancro-Associazione Italiana per la Ricerca sul Cancro (FIRC-AIRC). A.N.D. and M.M. were supported by the Ministry of Education, Youth, and Sports of the Czech Republic (CEITEC 2020 LQ1601). D.A.P. was supported by a Wellcome Trust Senior Investigator Award (100326/Z/12/Z). D.M.C. was supported by the Ministry of Health of the Russian Federation (0908300057056). The purchase of a FACSSymphony A5 was defrayed in part by a grant from the Italian Ministry of Health (Agreement 82/2015).",
year = "2020",
doi = "10.1038/s41590-020-0791-5",
language = "English",
volume = "21",
pages = "1552--1562",
journal = "Nat. Immunol.",
issn = "1529-2908",
publisher = "Nature Research",
number = "12",
}